Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy

Endocrine Reviews

Volumn 24, Issue 6, 2003, Pages 802-835

  Prabhakar, Bellur S ^a   Bahn, Rebecca S ^b   Smith, Terry J ^c,d  

^a UNIVERSITY OF ILLINOIS   (United States)

^b MAYO CLINIC   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d VA LONG BEACH HEALTHCARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; CHEMOKINE; COMPLEMENTARY DNA; CYTOKINE; THYROTROPIN RECEPTOR;

AUTOIMMUNE DISEASE; B LYMPHOCYTE; ENVIRONMENTAL FACTOR; EXTRAOCULAR MUSCLE; EYE DISEASE; FIBROBLAST; GRAVES DISEASE; HEREDITY; HUMAN; HYPERTHYROIDISM; LYMPHOCYTE; MOLECULAR CLONING; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SKIN DISEASE; T LYMPHOCYTE;

AUTOANTIGENS; AUTOIMMUNITY; CONNECTIVE TISSUE; ENVIRONMENT; FIBROBLASTS; GLYCOSAMINOGLYCANS; GRAVES DISEASE; HUMANS; ORBIT; RECEPTORS, THYROTROPIN; RISK FACTORS; THYROID GLAND;

EID: 0346057834     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2002-0020     Document Type: Review

References (345)

1. Bartels ED 1941 Heredity in Graves' disease. Copenhagen: Enjnar Munksgaards Forlag
2. Brix TH, Christensen K, Holm NV, Harvald B, Hegedus L 1998 A population-based study of Graves' disease in Danish twins. Clin Endocrinol 48:397-400
3. Brix TH, Kyvik KO, Christensen K, Hegedus L 2001 Evidence for a major role of heredity in Graves' disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab 86:930-934
4. Grumet FC, Payne RO, Konishi J, Kriss JP 1974 HLA antigens as markers for disease susceptibility and autoimmunity in Graves' disease. J Clin Endocrinol Metab 39:1115-1119
5. Farid NR, Stone E, Johnson G 1980 Graves' disease and HLA: clinical and epidemiologic associations. Clin Endocrinol (Oxf) 13:535-544
6. Mangklabruks A, Cox N, DeGroot LJ 1991 Genetic factors in autoimmune thyroid disease analyzed by restriction fragment length polymorphisms of candidate genes. J Clin Endocrinol Metab 73:236-244
7. Yanagawa T, Mangklabruks A, Chang Y-B, Okamoto Y, Fisfalen M-E, Curran PG, DeGroot LJ 1993 Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to Graves' disease in a Caucasian population. J Clin Endocrinol Metab 76:1569-1574
8. Yanagawa T, Mangklabruks A, DeGroot LJ 1994 Strong association between HLA-DQA1*0501 and Graves' disease in a male Caucasian population. J Clin Endocrinol Metab 79:227-229
9. Chen Q-Y, Huang W, She J-X, Baxter F, Volpe R, MacLaren NK 1999 HLA-DRB1*08, DRB1*03/DRB3*0101, and DRB3*0202 are susceptibility genes for Graves' disease in North American Caucasians, whereas DRB1*07 is protective. J Clin Endocrinol Metab 84:3182-3186
10. Tomer Y, Davies TF 2000 The genetics of familial and non-familial hyperthyroid Graves' disease. In: Rapoport B, McLachlan SM, eds. Graves' disease: pathogenesis and treatment. Boston: Kluwer Academic Publishers; 19-41
11. Tomer Y, Davies TF 2002 Genetic factors relating to the thyroid with emphasis on complex diseases. In: Waas JAH, Shalet SM, eds. Oxford textbook of endocrinology and diabetes. Oxford, UK: Oxford University Press; 351-366
12. Walker LSK, Abbas AK 2002 The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol 2:11-19
13. Donner H, Rau H, Walfish PG, Braun J, Siegmund T, Finke R, Herwig J, Usadel KH, Badenhoop K 1997 CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus. J Clin Endocrinol Metab 82:143-146
14. Yanagawa T, Hidaka Y, Guimaraes V, Soliman M, DeGroot LJ 1995 CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population. J Clin Endocrinol Metab 80:41-45
15. Yanagawa T, Taniyama M, Enomoto S, Gomi K, Maruyama H, Ban Y, Saruta T 1997 CTLA4 gene polymorphism confers susceptibility to Graves' disease in Japanese. Thyroid 7:843-846
16. Heward JM, Allahabadia A, Armitage M, Hattersley A, Dodson PM, Macleod K, Carr-Smith J, Daykin J, Daly A, Sheppard MC, Holder RL, Barnett AH, Franklyn JA, Gough SC 1999 The development of Graves' disease and the CTLA-4 gene on chromosome 2q33. J Clin Endocrinol Metab 84:2398-2401
17. Vaidya B, Imrie H, Perros P, Young ET, Kelly WF, Carr D, Large DM, Toft AD, McCarthy MI, Kendall-Taylor P, Pearce SH 1999 The cytotoxic T lymphocyte antigen-4 is a major Graves' disease locus. Hum Mol Genet 8:1195-1199
18. Kouki T, Sawai Y, Gardine C, Fisfalen M-E, Alegre M-L, DeGroot LJ 2000 CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. J Immunol 165:6606-6611
19. Weetman AP, Ajjan RA, Watson PF 1997 Cytokines and Graves' disease. Baillieres Clin Endocrinol Metab 11:481-497
20. Notkins AL, Onodera T, Prabhakar BS 1984 Virus-induced autoimmunity. In: Notkins AL, Oldstone MBA, eds. Concepts in viral pathogenesis. New York: Springer-Verlag; 210-215
21. Abe J, Kotzin BL, Jujo K, Melish ME, Glode MP, Leung DYM 1992 Selective expansion of T cells expressing Vβ2 and Vβ8 in Kawasaki disease. Proc Natl Acad Sci USA 89:4066-4070
22. Paliard X, West SG, Lafferty JA, Clements JR, Kappler JW, Marrack P, Kotzin BL 1991 Evidence for the effects of a superantigen in rheumatoid arthritis. Science 253:325-329
23. Tomai MA, Beachey EH, Majumdar G, Kotb M 1992 Metabolically active antigen presenting cells are required for human T cell proliferation in response to the superantigen streptococcal M protein. FEMS Microbiol Immunol 89:155-164
24. Tumang JR, Posnett DN, Cole BC, Crow M, Friedman SM 1990 Helper T cell dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge. J Exp Med 171:2153-2158
25. Mourad W, Scholl P, Diaz A, Geha R, Chatila T 1989 The TSST-1 triggers B cell proliferation and differentiation via major histocompatibility complex unrestricted cognate T/B cell interaction. J Exp Med 170:2011-2022
26. Stuart PM, Woodward JG 1992 Yersinia enterocolitica produces superantigenic activity. J Immunol 148:225-233
27. Uchiyama T, Miyoshi-Akiyoma T, Kato H, Fijimaki W, Yan X 1993 Superantigenic properties of a novel mitogenic substance produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic symptoms. J Immunol 151:4407-4413
28. Sheldon P 1985 Specific cell-mediated responses to bacterial antigens and clinical correlations in reactive arthritis, Reiter's syndrome and ankylosing spondylitis. Immunol Rev 86:5-25
29. Lahesmaa R, Shurnik M, Vaara M, Leirisalo-Repo M, Nissila M, Gransfors K, Toivanen P 1991 Molecular mimicry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella with the same region of HLA a1-helix. Clin Exp Immunol 86:399-405
30. Fujinami RS, Oldstone, MBA 1985 Amino acid homology between the enchalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:1043-1046
31. Saegusa J, Prabhakar BS, Essani K, McClintock PR, Notkins AL 1986 Monoclonal antibody to Coxsackie virus B4 reacts with myocardium. J Infect Dis 153:372-378
32. Fujinami RS, Nelson JA, Walker L, Oldstone MBA 1988 Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR βa chain: a means for graft rejection and immunosuppression. J Virol 62:100-105
33. Beisel KW, Srinivasappa J, Prabhakar BS 1991 Identification of a putative shared epitope between Coxsackie virus B4 and α cardiac myosin heavy chain. Clin Exp Immunol 86:49-57
34. Cox SP, Phillips DI, Osmond C 1989 Does infection indicate Graves' disease? A population based 10 year study. Autoimmunity 4:43-49
35. Phillips DI, Barker DJ, Smith BR, Didcote S, Morgan D 1985 The geographical distribution of thyrotoxicosis in England according to the presence or absence of TSH-receptor antibodies. Clin Endocrinol (Oxf) 23:283-287
36. Toft AD, Blackwell CC, Saadi AT, Wu P, Lymberi P, Soudjidelli M, Weir DM 1990 Secretor status and infection in patients with Graves' disease. Autoimmunity 7:279-289
37. Collier A, Patrick AW, Toft AD, Blackwell CC, James VS, Weir DM 1988 Increased prevalence of non-secretors in patients with Graves' disease-evidence for an infective aetiology? Br Med J 296:1162-1165
38. Valtonen VV, Ruutu P, Varis K, Ranki M, Malkamaki M, Makela PH 1986 Serological evidence for the role of bacterial infections in the pathogenesis of thyroid diseases. Acta Med Scand 219:105-111
39. Luo G, Fan JL, Seetharamaiah GS, Desai RK, Dallas JS, Wagle NM, Doan R, Niesel DW, Klimpel GR, Prabhakar BS 1993 Immunization of mice with Yersinia enterocolitica leads to the induction of antithyrotropin receptor antibodies. J Immunol 151:922-928
40. Luo G, Seetharamaiah GS, Niesel DW, Peterson JW, Prabhakar BS, Klimpel GR 1994 Purification and characterization of Yersinia enterocolitica envelope proteins that induce antibodies which react with the human thyrotropin receptor. J Immunol 152:2555-2561
41. Tomer Y, Davies TF 1993 Infection, thyroid disease and autoimmunity. Endocr Rev 14:107-120
42. Bech K, Larsen JH, Hansen JM, Nerup J 1974 Yersinia enterocolitica infection and thyroid disorder. Lancet 2:91-95
43. Weiss M, Rubinstein E, Bottone EJ, Shenkman L, Bank H 1979 Yersinia enterocolitica antibodies in thyroid disorder. Isr J Med Sci 15:553-555
44. Shenkman L, Bottone EJ 1981 Antibodies to Yersinia enterocolitica in thyroid disease. Ann Intern Med 85:735-739
45. Shenkman L, Bottone EJ 1981 The occurrence of antibodies to Yersinia enterocolitica in thyroid disease. In: Bottone EJ, ed. Yersinia enterocolitica. Chap 13. Boca Raton, FL: CRC Press; 135-144
46. Weiss P, Ingbar SH, Winblad S, Kasper DL 1983 Demonstration of a saturable binding site for thyrotrophin in Yersinia enterocolitica. Science 219:1331-1333
47. Heyman P, Harrison LC, Robins-Browne R 1986 Thyrotropin (TSH) binding sites on Yersinia enterocolitica recognized by immunoglobulins from humans with Graves' disease. Clin Exp Immunol 64:249-254
48. Franke TF, Wenzel BE 1991 A molecular basis for antigen homologies of thyroid epithelial cells and plasmid-encoded proteins of enteropathogenic Yersinia enterocolitica. Contrib Microbiol Immunol 12:89-92
49. Wenzel BE, Heesemann J, Wenzel KW, Scriba PC 1988 Antibodies to plasmid-encoded proteins of enteropathogenic Yersinia in patients with autoimmune thyroid disease. Lancet 1:56
50. Wenzel BE, Heesemann J, Wenzel KW, Scriba PC 1988 Patients with autoimmune thyroid diseases have antibodies to plasmid encoded proteins of enteropathogeinc Yersinia. J Endocrinol Invest 11:139-141
51. Arscott P, Rosen ED, Konig RJ, Kaplan M, Ellis T, Baker Jr JE 1992 Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease. J Clin Endocrinol Metab 75:295-300
52. Ebner S, Alex S, Klugman T, Appel M, Heesemann J, Wenzel B 1991 Immunization with Yersinia enterocolitica purified outer membrane protein induces lymphocyric thyroiditis in the BB/WOR rat. Thyroid 1(Suppl 1):S28 (Abstract)
53. Bech K, Clemmensen O, Larsen JH, Bendixen G 1977 Thyroid disease and Yersinia. Lancet 1:1060-1061
54. Burman KD, Lukes YG, Gemiski P 1991 Molecular homology between the human TSH receptor and Yersinia enterocolitica. Thyroid 1(Suppl 1):S62 (Abstract)
55. Seetharamaiah GS, Desai RK, Dallas JS, Tahara K, Kohn LD, Prabhakar BS 1993 Induction of TSH binding inhibitory immunoglobulins with the extracellular domain of human thyrotropin receptor produced using a baculovirus vector. Autoimmunity 14:315-320
56. Seetharamaiah GS, Kurosky A, Desai RK, Dallas JS, Prabhakar BS 1994 A recombinant extracellular domain of the thyrotropin receptor binds thyrotropin in the absence of membranes. Endocrinology 134:549-554
57. Wagle NM, Dallas JS, Seetharamaiah GS, Fan JL, Desai RK, Memar O, Rajaraman S, Prabhakar BS 1994 Induction of hyperthyroxinemia in BALB/c but not in other strains of mice. Autoimmunity 18:103-112
58. Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Justement LB, Prabhakar BS, Klimpel GR 1996 Yersinia enterocolitica envelope proteins that are cross-reactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity. J Autoimmun 9:509-516
59. Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Prabhakar BS, Klimpel GR 1997 Lipoprotein from Yersinia enterocolitica contains epitopes that crossreact with the human thyrotropin receptor. J Immunol 158:1976-1983
60. Benoist C, Mathis D 2001 Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? Nat Immunol 2:797-801
61. Adams DD, Purves HD 1956 Abnormal responses in the assay of thyrotropin. Proc Univ Otago Med Sch 34:11-12
62. McKenzie JM 1958 The bioassay of thyrotropin in serum. Endocrinology 63:372-382
63. McKenzie JM 1962 Fractionation of plasma containing the long-acting thyroid stimulator. J Biol Chem 237:3571-3572
64. Kriss JP 1968 Inactivation of long-acting thyroid stimulator (LATS) by anti-κ and anti-λ antisera. J Clin Endocrinol Metab 28:1440-1444
65. Smith BR, Dorrington KJ, Munro DS 1969 The distribution of the long-acting thyroid stimulator among γ G immunoglobulins. Biochem Biophys Acta 188:89-100
66. Manley SW, Bourke JR, Hawker RW 1974 The thyrotropin receptor in guinea pig thyroid homogenate: interaction with the long-acting thyroid stimulator. J Endocrinol 61:437-445
67. Adams DD, Kennedy TH 1967 Occurrence in thyrotoxicosis of a y globulin which protects LATS from neutralization by an extract of thyroid gland. J Clin Endocrinol Metab 27:173-177
68. Kraiem Z, Lahat N, Glaser B, Baron E, Sadoh O, Sheinfeld M 1987 Thyrotropin receptor blocking antibodies: incidence, characterization and in vitro synthesis. Clin Endocrinol (Oxf) 27:409-421
69. Kohn LD, Valente WA, Laccetti P, Cohen JL, Aloj SM, Grollman EF 1983 Multicompetent structure of the thyrotropin receptor: relationship to Graves' disease. Life Sci 32:15-30
70. Martino E, Pinchera A, Capiferri R, Macchia E, Sardano G, Bartalena L, Mazzanti F, Baschieri L 1976 Dissociation of responsiveness in thyrotropin-releasing hormone and thyroid suppressibility following antithyroid drug therapy in hyperthyroidism. J Clin Endocrinol Metab 43:543-549
71. Drexhage H, Bottazzo G, Doniach D, Bitensky L, Chayen J 1980 Evidence for thyroid-growth-stimulating immunoglobulins in some goitrous thyroid diseases. Lancet ii:287-292
72. Orgiazzi J, Williams DE, Chopra IJ, Solomon DH 1976 Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease. J Clin Endocrinol Metab 42:341-354
73. Kraiem Z, Baron E, Kahana L, Sadeh O, Sheinfeld M 1992 Changes in the stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism. Clin Endocrinol (Oxf) 36:211-214
74. Weetman AP, Yatenman ME, Ealey PA, Black CM, Reimer CB, Williams Jr RC, Shine B, Marshall MJ 1990 Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. J Clin Invest 86:723-727
75. Davies TF, Weber CM, Wallack P, Platzer M 1986 Restricted heterogeneity and T cell dependence of human thyroid autoantibody immunoglobulin G subclasses. J Clin Endocrinol Metab 62:945-949
76. Parks VA, McLachlan SM, Bird P, Rees Smith B 1984 Distribution of microsomal antibody and thyroglobulin antibody activity amongst IgG subclasses. Clin Exp Immunol 57:239-243
77. McKenzie JM 1958 Delayed thyroid response to serum from thyrotoxic patients. Endocrinology 62:865-868
78. Adams DD 1958 The presence of an abnormal thyroid-stimulating hormone in the serum of some thyrotoxic patients. J Clin Endocrinol Metab 18:699-712
79. Strakosch CR, Wenzel BE, Row W, Volpe R 1982 Immunology of autoimmune thyroid disease. N Engl J Med 307:1499-1507
80. Volpe R 1988 The immunoregulatory disturbance in autoimmune thyroid disease. Autoimmunity 2:55-72
81. Iwatani Y, Amino N, Mori H, Asari S, Izumiguchi Y, Kumahara Y, Miyai K 1983 T lymphocyte subsets in autoimmune thyroid diseases and subacute thyroiditis detected with monoclonal antibodies. J Clin Endocrinol Metab 56:251-254
82. Wall J, Baur R, Schleusener H, Bandy-Defoe P 1983 Peripheral blood and intrathyroidal mononuclear cell populations in patients with autoimmune thyroid disorders enumerated using monoclonal antibodies. J Clin Endocrinol Metab 56:164-169
83. Jackson RA, Haynes BF, Burch WM, Shimizu K, Bowring MA, Eisenbarth GS 1984 Ia+ T cells in new onset Graves' disease. J Clin Endocrinol Metab 59:187-190
84. Davies TF, Martin A, Conception ES, Graves P, Cohen L, Ben-Nun A 1991 Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease. N Engl J Med 325:238-244
85. Davies TF, Martin A, Conception ES, Graves P, Lahat N, Cohen WL, Ben-Nun A 1992 Widespread V β and preferential V α T cell receptor gene utilization by intrathyroidal T cells in human autoimmune thyroid disease. J Clin Invest 89:157-162
86. Dayan CM, Londei M, Corcoran AE, Grubeck-Loebenstein B, James RFL, Rapoport B, Feldman M 1991 Autoantigen recognition by thyroid infiltrating T cells in Graves' disease. Proc Natl Acad Sci USA 88:7415-7419
87. Gulwani-Akolkar B, Posnett DN, Janson CH, Grunewald J, Wigzel H, Akolar P, Gregersen APK, Silver J 1991 T cell receptor V gene segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. J Exp Med 174:1139-1146
88. McKenzie JM 1968 Humoral factors in the pathogenesis of Graves' disease. Physiol Rev 48:252-309
89. Rose NR 1988 Autoimmunity: a personal memoir. Autoimmunity 1:15-21
90. Weetman AP, McGregor AM 1994 Autoimmune thyroid disease: further developments in our understanding. Endocr Rev 15:788-830
91. Akamizu T, Mori T, Ishii H, Yotota T, Nakamura H, Imura H 1988 Purification of TSH receptor from porcine thyroid membrane and effect of various protease inhibitors on receptor stability. Endocrinol Jpn 35:275-283
92. Giordano C, Richiusa P, Bagnasco M, Pizzolanti G, Di Biasi F, Sbriglia MS, Mattina A, Pesce G, Montagna P, Capone F, Misiano G, Scorsone A, Pugliese A, Galluzo A 2001 Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease. Thyroid 11:233-244
93. Baker Jr JR 2001 The nature of apoptosis in the thyroid and the role it may play in autoimmune thyroid disease. Thyroid 11:245-247
94. Stassi G, De Maria R 2002 Autoimmune thyroid disease: new models of cell death in autoimmunity. Nat Rev Immunol 2:195-204
95. Parmentier M, Libert F, Maenhut C, Lefort A, Gerard C, Perret J, Van Sande J, Dumont JE, Vassart G 1989 Molecular cloning of the thyrotropin receptor. Science 246:1620-1622
96. Nagayama Y, Kaufman DD, Seto P, Rapoport B 1989 Molecular cloning, sequence, and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Comm 165:1184-1190
97. Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE, Vassart G 1989 Cloning sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies. Biochem Biophys Res Comm 165:1250-1255
98. Misrahi M, Loosflet H, Atger M, Sar S, Guiochon-Mante, A, Milgrom E 1990 Cloning, sequencing and expression of human TSH receptor. Biochem Biophys Res Comm 166:394-403
99. Nagayama Y, Rapoport B 1992 The thyrotropin receptor 25 years after its discovery: new insight after its molecular cloning. Mol Endocrinol 6:145-156
100. Vassart G, Dumont J 1992 The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev 13:596-611
101. Kohn LD, Kosugi S, Ban T, Saji M, Ikuyama S, Giuliani C, Hidaka A, Shimura H, Akamizu T, Tahara K 1992 Molecular basis for the auto reactivity against thyroid stimulating hormone receptor. Int Rev Immunol 9:135-165
102. Prabhakar BS, Seetharamaiah GS, Fan J-L 1997 Thyrotropin receptor mediated diseases - a paradigm for receptor autoimmunity. Immunol Today 18:437-442
103. Rapoport B, Chazenbalk GD, Jaume JC, McLachlan, SM 1998 The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev 19:678-716
104. Chazenbalk GD, Rapoport B 1995 Expression of the extracellular domain of the thyrotropin receptor in the baculovirus system using a promoter active earlier than the polyhedrin promoter: implications for the expression of functional, highly glycosylated proteins. J Biol Chem 270:1543-1549
105. Seetharamaiah GS, Dallas JS, Patibandla SA, Thotakara RN, Prabhakar BS 1997 Requirement of glycosylation of the human thyrotropin receptor ectodomain for its reactivity with autoantibodies in patients' sera. J Immunol 158:2798-2804
106. Rapoport B, McLachlan SM 2001 Thyroid autoimmunity. J Clin Invest 108:1253-1259
107. Kajita Y, Rickards CR, Buckland PR, Howells RD, Rees Smith B 1985 Analysis of thyrotropin receptors by photoaffinity labeling. Orientation of receptor subunits in the cell membrane. Biochem J 227:413-420
108. Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E 1992 Two-subunit structure of the human thyrotropin receptor. Proc Natl Acad Sci USA 89:3765-3769
109. Chazenbalk GD, Pichurin P, Chen CR, Latrofa F, Johnstone AP, McLachlan SM, Rapoport B 2002 Thyroid-stimulating autoantibodies in Graves' disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor. J Clin Invest 110:161-164
110. Hoglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D 1999 Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med 189:331-339
111. Andre I, Gonzalez A, Wang B, Katz J, Benoist C, Mathis D 1996 Checkpoints in the progression of autoimmune disease: lessons from diabetes models. Proc Natl Acad Sci USA 93:2260-2263
112. Jenkins MK, Schwartz RH 1987 Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 165:302-319
113. + T cells from tolerance induction by the superantigen staphylococcal enterotoxin B. Eur J Immunol 26:858-862
114. Krummel MF, Allison JP 1995 CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182:459-465
115. Walunas TL, Bakker CY, Bluestone JA 1996 CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med 183:2541-2550
116. Perez VL, Van Parijs L, Biuckians A, Zheng XX, Strom TB, Abbas AK 1997 Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 6:411-417
117. Walunas TL, Bluestone JA 1998 CTLA-4 regulates tolerance induction and T cell differentiation in vivo. J Immunol 160:3855-3860
118. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH 1995 Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3:541-547
119. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW 1995 Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270:985-988
120. Lechner O, Lauber J, Franzke A, Sarukhan A, von Boehmer H, Buer J 2001 Fingerprints of anergic T cells. Curr Biol 11:587-595
121. Nishimura H, Nose M, Hiai H, Minato N, Honjo T 1999 Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141-151
122. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Kara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo 2001 Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319-322
123. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T 2000 Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027-1034
124. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ 2001PD-L2 is a second ligand for PD-I and inhibits T cell activation. Nat Immunol 2:261-268
125. Chambers CA 2001 The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol 22:217-223
126. H2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. J Immunol 164:3563-3572
127. H2, cells secrete multiple chemokines and promote rapid induction of autoimmune diabetes. J Immunol 162:2511-2520
128. H2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice. J Exp Med 186:299-306
129. H2 bias. J Neuroimmunol 100:64-73
130. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S 1992 Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314-317
131. Sobel ES, Kakkanaiah VN, Cohen PL, Eisenberg RA 1993 Correction of gld autoimmunity by co-infusion of normal bone marrow suggests that gld is a mutation of the Fas ligand gene. Int Immunol 5:1275-1278
132. Suda T, Takahashi T, Golstein P, Nagata S 1993 Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75:1169-1178
133. Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM 1995 Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81:935-946
134. Marion S, Braun JM, Ropars A, Kohn LD, Charreire, J 1994 Induction of autoimmunity by immunization of mice with human thyrotropin receptor. Cell Immunol 158:329-341
135. Costagliola S, Alcalde L, Tonacchera M, Ruf J, Vassart G, Ludgate M 1994 Induction of thyrotropin receptor (TSH-R) autoantibodies and thyroiditis in mice immunized with the recombinant TSH-R. Biochem Biophys Res Comm 199:1027-1034
136. Costagliola S, Many MC, Stalmans-Falys M, Tonacchera M, Vassart G, Ludgate M 1994 Recombinant thyrotropin receptor and the induction of autoimmune thyroid disease in BALB/c mice: a new animal model. Endocrinology 135:2150-2159
137. Costagliola S, Many MC, Stalmans-Falys M, Vassart G, Ludgate M 1995 The autoimmune response induced by immunizing female mice with recombinant human thyrotropin receptor varies with the genetic background. Mol Cell Endocrinol 115:199-206
138. Costagliola S, Many MC, Stalmans-Falys M, Vassart G, Ludgate M 1996 Transfer of thyroiditis with syngeneic spleen cells sensitized with the human thyrotropin receptor, to naive BALB/c and NOD mice. Endocrinology 137:4637-4639
139. Ludgate M 2000 Animal models of Graves' disease. Eur J Endocrinol 142:1-8
140. Lanzaveccha A 1990 Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol 8:773-793
141. MacLennan ICM, Gulbranson-Judge A, Toellner KM, Casamayor-Palleja M, Chan E, Sze DMY, Luther SA, Orbea HA 1997 The changing preference of T and B cells for partners as T-dependent antibody responses develop. Immunol Rev 156:53-56
142. Parker DC 1993 T cell-dependent B-cell activation. Annu Rev Immunol 11:331-340
143. Carayanniotis G, Huang GC, Nicholson LB, Scott T, Allain P, McGregor AM, Banga JP 1995 Unaltered thyroid function in mice responding to a highly immunogenic thyrotropin receptor: implications for the establishment of a mouse model for Graves' disease. Clin Exp Immunol 99:294-302
144. Vlase H, Nakashima M, Graves PN, Tomer Y, Morris JC, Davies TF 1995 Defining the major antibody epitopes on the human thyrotropin receptor in immunized mice: evidence for intramolecular epitope spreading. Endocrinology 136:4415-4419
145. Vlase H, Weiss M, Graves PN, Davies TF 1998 Characterization of the murine immune response to the murine TSH receptor ectodomain: induction of hypothyroidism and TSH receptor antibodies. Clin Exp Immunol 113:111-118
146. Shimojo N, Kohno Y, Yamaguchi KK, Kikuoka SI, Hoshioka A, Miimi H, Hirai A, Tamura Y, Saito Y, Kohn LD, Tahara K 1996 Induction of Grave's-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule. Proc Natl Acad Sci USA 93:11074-11079
147. Kikuoka SI, Shimojo N, Yamaguchi KK, Watanabe Y, Hoshioka A, Hirai A, Saito Y, Tahara K, Kohn LD, Maruyama N, Kohno Y, Niimi H 1998 The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model requires the N-terminal segment of the TSHR extracellular domain. Endocrinology 139:1891-1898
148. Yamaguchi KK, Shimojo N, Kikuoka SI, Hoshioka A, Hirai A, Tahara K, Kohn LD, Kohno Y, Niimi H 1997 Genetic control of anti-thyrotropin receptor antibody generation in H-2K mice immunized with thyrotropin receptor-transfected fibroblasts. J Clin Endocrinol Metab 82:4266-4269
149. Kita M, Ahmad L, Marians RC, Vlase H, Unger P, Graves PN, Davies TF 1999 Regulation and transfer of a murine model of thyrotropin receptor antibody. Endocrinology 140:1392-1398
150. Patibandla SA, Wagle NM, Seetharamaiah GS, Fan JL, Dallas JS, Prabhakar BS 1996 Experimental autoimmunity to thyrotropin receptor. Exp Clin Endocrinol Diabetes 104 (Suppl 3):28-32
151. Saipatibandla A, Prabhakar BS 1997 Autoimmunity to thyrotropin receptor. In: Klein JR, ed. Advances in neuroimmunology. Vol 6. London: Elsevier Science, Ltd.; 347-357
152. Bottazzo GG, Todd I, Mirakian R, Belfiore A, Pujol-Borrell R 1986 Organ-specific autoimmunity: a 1986 overview. Immunol Rev 94:137-169
153. Suri A, Katz JD 1999 Dissecting the role of CD4+ T cells in autoimmune diabetes through the use of TCR transgenic mice. Immunol Rev 169:55-65
154. O'Garra A, Arai N 2000 The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends Cell Biol 10:542-550
155. Germain RN, Ashwell DJ, Lechler RI, Margulies DH, Nickerson KM, Suzuki G, Tou JYL 1985 "Exon-shuffling" maps control of antibody-and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A β. Proc Natl Acad Sci USA 82:2940-2944
156. Costagliola S, Rodien P, Many MC, Ludgate M, Vassart G 1998 Genetic immunization against the human thyrotropin receptor causes thyroiditis and allows production of monoclonal antibodies recognizing the native receptor. J Immunol 160:1458-1465
157. Costagliola S, Pohlenz J, Refetoff S, Vassart G 1998 Generation of a murine model of Graves' disease by genetic immunization of outbred mice with human TSH receptor. J Endocrinol Invest 21:S4
158. Pichurin P, Pichurina O, Chazenbalk D, Paras C, Chen CR, Rapoport B, McLachlan SM 2002 Immune deviation away from Th1 in interferon-γ knockout mice does not enhance TSH receptor antibody production after naked DNA vaccination. Endocrinology 143:1182-1189
159. Nagayama Y, Kita-Furuyama M, Ando T, Nakao K, Mizuguchi H, Hayakawa T, Eguchi K, Niwa M 2002 A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor. J Immunol 168:2789-2794
160. Kaithamana S, Fan JL, Osuga Y, Shan-Guang L, Prabhakar BS 1999 Induction of experimental autoimmune Graves' disease in BALB/c mice. J Immunol 163:5157-5164
161. James JA, Harley JB 1998 B-cell epitope spreading in autoimmunity. Immunol Rev 164:185-200
162. McCluskey J, Farris DA, Keech CL, Purcell AW, Rischmueller M, Kinoshita
163. Vincent A, Willcox N, Hill M, Curnow J, MacLennan C, Beeson D 1998 Determinant spreading and immune responses to acetylcholine receptors in myasthenia gravis. Immunol Rev 164:157-168
164. Singh RR, Hahn BH 1998 Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis. Immunol Rev 164:201-208
165. Bahn RS 1995 Assessment and management of the patient with Graves' ophthalmopathy. Endocr Pract 1:172-178
166. Werner SC, Coleman DJ, Fravzen LA 1974 Ultrasonographic evidence of a consistent orbital involvement in Graves' disease. N Engl J Med 290:1447-1450
167. Salvi M, De Chiara F, Gardini E, Minelli R, Bianconi L, Alinovi A, Ricci R, Neri F, Tosi C, Roti E 1994 Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease. Eur J Endocrinol 131:113-119
168. Salvi M, Zhang Z-G, Haegert D, Woo M, Liberman A, Cadarso L, Wall JR 1990 Patients with endocrine ophthalmopathy not associated with overt thyroid disease have multiple thyroid immunological abnormalities. J Clin Endocrinol Metab 70:89-94
169. Marcocci C, Bartelena L, Bogazzi FM, Panicucci M, Pinchera A 1989 Studies on the occurrence of ophthalmopathy in Graves' disease. Acta Endocrinol (Copenh) 120:473-478
170. Bahn RS, Heufelder AE 1993 Mechanisms of disease: pathogenesis of Graves' ophthalmopathy. N Engl J Med 329:1468-1475
171. Forbes G, Gorman CA, Brennan MD, Gehring DG, Ilstrup DM, Earnest F 1986 Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle. AJNR 7:651-656
172. Tallstedt L, Norberg R 1988 Immunohistochemical staining of normal and Graves' extraocular muscle. Invest Ophthalmol Vis Sci 29:175-184
173. Kahaly G, Forester G, Hansen C 1998 Glycosaminoglycans in thyroid eye disease. Thyroid 8:429-432
174. Hufnagel TJ, Hickey WF, Cobbs WH, Jakobiec FA, Iwamoto T, Eagle RC 1984 Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with Graves' disease. Ophthalmology 91:1411-1419
175. Inoue D, Sato K, Maeda M, Inoko H, Tsuji K, Mori T, Imura H 1991 Genetic differences shown by HLA typing among Japanese patients with euthyroid Graves' ophthalmopathy, Graves' disease and Hashimoto's thyroiditis: genetic characteristics of euthyroid Graves' ophthalmopathy. Clin Endocrinol (Oxf) 34:57-62
176. Frecker M, Stenszky V, Balazs C, Kozma L, Kraszits E, Faria NR 1986 Genetic factors in Graves' ophthalmopathy. Clin Endocrinol (Oxf) 25:479-485
177. Weetman AP, Zhang L, Webb S, Shine B 1990 Analysis of HLA-DQB and HLA-DPB alleles in Graves' disease by oligonucleotide probing of enzymatically amplified DNA. Clin Endocrinol (Oxf) 33:65-71
178. Frecker M, Mercer G, Skanes VM, Farid NR 1988 Major histocompatibility complex (MHC) factors predisposing to and protecting against Graves' eye disease. Autoimmunity 1:307-315
179. Payami H, Joe S, Farid NR, Stenszky V, Chan SH, Yeo PP, Cheah JS, Thomson G 1989 Relative predispositional effects (RPEs) of marker allele with disease: HLA-DR alleles and Graves' disease. Am J Hum Genet 45:541-546
180. Weetman AP, So AK, Warner CA, Foroni L, Fells P, Shine B 1988 Immunogenetics of Graves' ophthalmopathy. Clin Endocrinol (Oxf) 28:619-628
181. Blakemore AIF, Watson PF, Weetman AP, Duff SW 1995 Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene. J Clin Endocrinol Metab 80:111-115
182. Cuddihy RM, Bahn RS 1996 Lack of an association between alleles of interleukin-1 and interleukin-1 receptor antagonist genes and Graves' disease in a North American Caucasian population. J Clin Endocrinol Metab 81:4476-4478
183. Mühlberg T, Kirchberger M, Spitzweg C, Herrmann F, Heberling H-J, Heufelder AH 1998 Lack of association of Graves' disease with the A2 allele of the interleukin-1 receptor antagonist gene in a white European population. Eur J Endocrinol 38:686-690
184. Siegmond T, Usadel KH, Donner H, Braun J, Walfish PG, Badenhoop K 1998 Interferon-γ gene micro satellite polymorphisms in patients with Graves' disease. Thyroid 8:1013-1017
185. Tomer Y, Barbesino G, Greenberg DA, Concepcion E, Davies TF 1999 Mapping the major susceptibility loci for familial Graves' and Hashimoto's diseases: evidence for genetic heterogeneity and gene interactions. J Clin Endocrinol Metab 84:4656-4664
186. Villanueva R, Inzerillo AM, Tomer Y, Barnesino G, Miltzer M, Concepcion ES, Greenberg DA, MacLaren N, Sun ZS, Zhang DM, Tucci S, Davies TF 2000 Limited genetic susceptibility to severe Graves' ophthalmopathy: no role for CTLA-4 but evidence for an environmental etiology. Thyroid 10:791-798
187. Prummel MF, Wiersinga WM 1993 Smoking and risk of Graves' disease. JAMA 269:479-482
188. Hagg E, Asplund K 1987 Is endocrine ophthalmopathy related to smoking? Br Med J 295:634-635
189. Pfeilschifter J, Ziegler R 1996 Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs. lifetime cigarette consumption. Clin Endocrinol (Oxf) 45:477-481
190. Shine B, Fells P, Edwards OM, Weetman AP 1990 Association between Graves' ophthalmopathy and smoking. Lancet 335:1261-1263
191. Silman AJ 1993 Smoking and the risk of rheumatoid arthritis. J Rheumatol 20:1815-1816
192. Clakins BM 1989 A meta-analysis of the role of smoking in inflammatory bowel disease. Diag Dis Sci 34:1841-1854
193. Wakelkamp IM, Gerding MN, Van Der Meer JW, Prummel MF, Wiersinga WM 2000 Both Th1 and Th2 derived cytokines in serum are elevated in Graves' ophthalmopathy. Clin Exp Immunol 121:453-457
194. Salvi M, Girasole G, Pedrazzoni M, Passeri M, Giuliani N, Minelli R, Braverman LE, Roti E 1996 Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 in patients with Graves' disease. J Clin Endocrinol Metab 81:2976-2979
195. Metcalfe RA, Weetman AP 1994 Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia; possible role in thyroid-associated ophthalmopathy. Clin Endocrinol (Oxf) 40:67-72
196. Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, Saaf M, Hamberger B 1996 Graves' hyperthyroidism: treatment with anti-thyroid drugs, surgery, or radioiodine - a prospective, randomized study. J Clin Endocrinol Metab 81:2986-2993
197. Jones BM, Kwok CCH, Kung AWC 1999 Effect of radioactive iodine therapy on cytokine production in Graves' disease: transient increases in interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-α, with longer-term increases in interferon-γ production. J Clin Endocrinol Metab 84:4106-4110
198. Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, Taube A 1992 Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. N Engl J Med 326:1733-1738
199. Kung AWC, Ysu CC, Cheng A 1994 The incidence of ophthalmopathy after radioiodine therapy for Graves' disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab 79:542-546
200. Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell'Unto E, Bruno-Bossio G, Nardi M, Bartolomei MP, Lepri A, Rossi G, Martino E, Pinchera A 1998 Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med 338:73-78
201. Wiersinga WM 1998 Preventing Graves' ophthalmopathy. N Engl J Med 338:121-122
202. Weetman AP, Cohen S, Gatter KC, Fells P, Shine B 1989 Immunohistochemical analysis of the retrobulbar tissues in Graves' ophthalmopathy. Clin Exp Immunol 75:222-227
203. Heufelder AE, Bahn RS 1993 Elevated expression in situ of selectin and immunoglobulin superfamily adhesion molecules in retroocular connective tissues from patients with Graves' ophthalmopathy. Clin Exp Immunol 91:381-389
204. Heufelder AE, Bahn RS 1993 Detection and localization of cytokine immunoreactivity in retroocular connective tissue in Graves' ophthalmopathy. Eur J Clin Invest 23:10-17
205. Heufelder AE, Herterich S, Ernst G, Bahn RS, Scriba PC 1995 Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves' ophthalmopathy. Eur J Endocrinol 132:266-277
206. Heufelder AE, Wenzel BE, Scriba PC 1996 Antigen receptor variable region repertoires expressed by T cells infiltrating thyroid, retroorbital and pretibial tissue in Graves' disease. J Clin Endocrinol Metab 81:3733-3739
207. de Carli M, D'Elios M, Mariotti S, Marcocci C, Pinchera A, Ricci M, Romagnani S, del Prete G 1993 Cytolytic T cells with Th-1 like cytokine profile predominate in retroorbital lymphocytic infiltrates of Graves' ophthalmopathy. J Clin Endocrinol Metab 77:1120-1124
208. Hiromatsu Y, Yang D, Bednarczuk T, Miyake I, Nonaka K, Inoue Y 2000 Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 85:1194-1199
209. McLachlan SM, Prummel MF, Rapoport B 1994 Cell-mediated or humoral immunity in Graves' ophthalmopathy? Profiles of T-cell cytokines amplified by polymerase chain reaction from orbital tissue. J Clin Endocrinol Metab 78:1070-1074
210. + and specifically recognize autologous fibroblasts. J Clin Invest 93:2738-2743
211. Aniszewski JP, Valyasevi RW, Bahn RS 2000 Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy. J Clin Endocrinol Metab 85:776-780
212. Natt N, Bahn RS 1997 Cytokines in the evolution of Graves' ophthalmopathy. Autoimmunity 26:129-136
213. Heufelder AE 1997 Retro-orbital autoimmunity. Baillieres Clin Endocrinol Metab 11:499-520
214. Smith TJ, Wang HS, Evans CH 1995 Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts. Am J Physiol 268:C382-C388
215. Korducki JM, Loftus SJ, Bahn RS 1992 Stimulation of glycosaminoglycan production in cultured human retroocular fibroblasts. Invest Ophthalmol Vis Sci 33:2037-2042
216. Kaback LA, Smith TJ 1999 Expression of hyaluronan synthase messenger ribonucleic acids and their induction of interleukin-1β in human orbital fibroblasts: potential insight into the molecular pathogenesis of thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 84:4079-4084
217. 2 and hyaluronan synthesis. Endocrinology 140:3518-3525
218. Valyasevi RW, Jyonouchi SC, Dutton CM, Munsakul N, Bahn RS 2001 Effect of TNF-α, IFN-γ, TGF-β on adipogenesis and expression of TSH receptor in human orbital preadipocyte fibroblasts. J Clin Endocrinol Metab 86:903-908
219. Jyonouchi S, Valyasevi R, Harteneck DA, Dutton CM, Bahn RS 2001 Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves' ophthalmopathy. Thyroid 11:929-934
220. Heufelder AE, Bahn RS 1994 Modulation of Graves' orbital fibroblast proliferation by cytokines and glucocorticoid receptor agonists. Invest Ophthalmol Vis Sci 35:120-127
221. Ahmann A, Baker JR, Weetman AP, Wartofsky L, Nutman TB, Burman KD 1987 Antibodies to porcine eye muscle in patients with Graves' ophthalmopathy: identification of serum immunoglobulin directed against unique determinants by immunoblotting and enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 64:454-460
222. Miller A, Sikorska H, Salvi M, Wall JR 1986 Evaluation of an enzyme-linked immunosorbent assay for the measurement of autoantibodies against eye muscle antigens in Graves' ophthalmopathy. Acta Endocrinol 113:514-522
223. Weetman AP, Fells P, Shine B 1989 T and B cell reactivity to extraocular and skeletal muscle in Graves' ophthalmopathy. Br J Ophthalmol 73:323-327
224. Kadlubowski M, Irvine WJ, Rowland CA 1986 The lack of specificity of ophthalmic immunoglobulins in Graves' disease. J Clin Endocrinol Metab 63:990-995
225. Salvi M, Hiromatsu Y, Bernard N, How J, Wall JR 1988 Human orbital tissue and thyroid membrane express a 64 kDa protein which is recognized by autoantibodies in serum of patients with thyroid-associated ophthalmopathy. FEBS Lett 232:125-129
226. Salvi M, Bernard N, Miller A, Zhang ZG, Gardini E, Wall JR 1991 Prevalence of antibodies reactive with a 64 kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy. Thyroid 1:207-213
227. Bahn RS, Gorman CA, Johnson CM, Smith TJ 1989 Presence of antibodies in the sera of patients with Graves' disease recognizing a 23 kilodalton fibroblast protein. J Clin Endocrinol Metab 69:622-628
228. Dong Q, Ludgate M, Vassart G 1991 Cloning and sequencing of a novel 64-kDa autoantigen recognized by patients with autoimmune thyroid disease. J Clin Endocrinol Metab 72:1375-1381
229. Zhang Z-G, Dong Q, Rodien P, Alcalde L, Bernard N, Boucher A, Salvi M, Arthurs B, Vassart GM, Ludgate M, Wall JR 1992 Antibodies in the serum of patients with autoimmune thyroid disorders react with a recombinant 98 amino acid fragment of a full length 64 kDa eye muscle membrane protein which is also expressed in the thyroid. Autoimmunity 13:151-157
230. Ross PV, Koenig RJ, Arscott P, Ludgate M, Waier M, Nelson CC, Kaplan MM, Baker Jr JR 1993 Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease. J Clin Endocrinol Metab 77:433-438
231. Kubota S, Gunji K, Stolarski C, Kennerdell JS, Wall J 1998 Reevaluation of the prevalences of serum autoantibodies reactive with "64-kd eye muscle proteins" in patients with thyroid-associated ophthalmopathy. Thyroid 8:175-179
232. Kubota S, Gunj K, Ackrell BAC, Cochran G, Stolarski C, Wengrowicz S, Kennerdell JS, Hiromatsu Y, Wall J 1998 The 64-kilodalton eye muscle protein is the flavoprotein subunit of mitochondrial succinate dehydrogenase: the corresponding serum antibodies are good markers of an immune-mediated damage to the eye muscle in patients with Graves' hyperthyroidism. J Clin Endocrinol Metab 83:443-447
233. Gunji K, De Bellis A, Li AW, Yamada M, Kubota S, Ackrell G, Wengrowicz S, Bellastella A, Bizzarro A, Sinisi A, Wall JR 2000 Cloning and characterization of the novel thyroid and eye muscle shared protein G2s: autoantibodies against G2s are closely associated with ophthalmopathy in patients with Graves' hyperthyroidism. J Clin Endocrinol Metab 85:1641-1647
234. Kadluboswki M, Irvine WJ, Rowland AC 1987 Anti-muscle antibodies in Graves' ophthalmopathy. J Clin Lab Immunol 24:105-111
235. Ludgate M, Dong Q, Dreyfus PA, Zakut H, Taylor P, Vassart G, Soreq H 1989 Definition, at the molecular level, of a thyroglobulin- acetylcholinesterase shared epitope: study of its pathophysiological significance in patients with Graves' ophthalmopathy. Autoimmunity 3:167-176
236. Konishi J, Herman MM, Kriss JP 1974 Binding of thyroglobulin and thyroglobulin-antithyroglobulin immune complex to extraocular muscle membrane. Endocrinology 95:434-446
237. Marino M, Lisi S, Pinchera A, Mazzi B, Latrofa F, Sellari-Franceschini S, McCluskey RT, Chiovato L 2001 Identification of thyroglobulin in orbital tissues of patients with thyroid-associated ophthalmopathy. Thyroid 11:177-185
238. Weightman DR, Oerros P, Sherif IH, Kendall-Taylor P 1993 Autoantibodies to IGF-1 binding sites in the thyroid associated ophthalmopathy. Autoimmunity 16:251-257
239. Gerding MN, van der Meer JW, Broenink M, Bakker O, Wiersinga WM, Prummel MF 2000 Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy. Clin Endocrinol (Oxf) 52:267-271
240. McLachlan SM, Pegg CA, Atherton MC, Middleton SL, Dickinson A, Clark F, Proctor SJ, Proud G, Rees Smith B 1986 Subpopulations of thyroid autoantibody secreting lymphocytes in Graves' and Hashimoto thyroid glands. Clin Exp Immunol 65:319-328
241. Heufelder AF, Dutton CM, Sarkar G, Donovan KA, Bahn RS 1993 Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves' ophthalmopathy and pretibial dermopathy. Thyroid 3:297-300
242. Feliciello A, Porcellini A, Ciullo I, Bonavolonta G, Avvedimento EV, Fenzi G 1993 Expression of thyrotropin-receptor mRNA in healthy and Graves' retro-orbital tissue. Lancet 342:337-338
243. Mengistu M, Lukes YG, Nagy EV, Burch HB, Carr FE, Lahiri S, Burman KD 1994 TSH receptor gene expression in retroocular fibroblasts. J Endocrinol Invest 17:437-441
244. Bahn RS, Dutton CM, Natt N, Joba W, Spitzweg C, Heufelder AE 1998 Thyrotropin receptor expression in Graves' orbital adipose/ connective tissues: potential autoantigen in Graves' ophthalmopathy. J Clin Endocrinol Metab 83:998-1002
245. Crisp MS, Lane C, Halliwell M, Wynford-Thomas D, Ludgate M 1997 Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 82:2003-2005
246. Spitzweg C, Joba W, Hunt N, Heufelder AE 1997 Analysis of human thyrotropin receptor gene expression and immunoreactivity in human orbital tissue. Eur J Endocrinol 136:599-607
247. Rapoport B, Alsabeth R, Aftergood D, McLachlan SM 2000 Elephantiasic pretibial myxedema: insight into and a hypothesis regarding the pathogenesis of the extrathyroidal manifestations of Graves' disease. Thyroid 10:685-692
248. Sorisky A, Pardasani D, Gagnon A, Smith TJ 1996 Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab 81:3428-3431
249. Valyasevi RW, Erickson DZ, Harteneck DA, Dutton CM, Heufelder AE, Jyonouchi SC, Bahn RS 1999 Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 84:2557-2562
250. Salvi M, Pedrazzoni M, Girasole G, Giuliana N, Minelli R, Wall JR, Roti E 2000 Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking. Eur J Endocrinol 143:197-202
251. Burnstine MA, Elner SG, Strieter RM, Kunkel SL, Elner VM 1999 Orbital fibroblast interleukin-6 gene expression and immuno-modulation. Ophthal Plast Reconstr Surg 15:306-311
252. Watson PF, Pickerill AP, Davies R, Weetman AP 1995 Semi-quantitative analysis of interleukin-1 α, interleukin-6 and interleukin-8 mRNA expression by human thyrocytes. J Mol Endocrinol 15:11-21
253. Haraguchi K, Shimura H, Ikeda M, Endo T, Onaya T 1998 Effects of cytokines on expression of thyrotropin receptor mRNA in rat preadipocytes. Thyroid 8:687-692
254. Shimura H, Miyazaki A, Haraguchi K, Endo T, Onaya T 1998 Analysis of differentiation-induced expression mechanisms of thyrotropin receptor gene in adipocytes. Mol Endocrinol 12:1473-1486
255. Haraguchi K, Shimura H, Lin L, Endo T, Onaya T 1996 Differentiation of rat adipocytes is accompanied by expression of thyrotropin receptors. Endocrinology 137:3200-3205
256. Sempowski GD, Rozenblit J, Smith TJ, Phipps RP 1998 Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production. Am J Physiol 274:C707-C714
257. Many MC, Costagliola S, Detrait M, Denef JF, Vassart G, Ludgate M 1999 Development of an animal model of autoimmune thyroid eye disease. J Immunol 162:4966-4974
258. Pichurin P, Van XM, Farilla L, Guo J, Chazenbalk GD, Rapoport B, McLachlan SM 2001 Naked TSH receptor DNA vaccination: a Th1 T cell response in which interferon-γ production, rather than antibody, dominates the immune response in mice. Endocrinology 142:3530-3536
259. Deleted in proof.
260. Otto EA, Ochs K, Hansen C, Wall JR, Kahaly GJ 1996 Orbital tissue-derived T lymphocytes from patients with Graves' ophthalmopathy recognize autologous orbital antigens. J Clin Endocrinol Metab 81:3045-3050
261. Arnold K, Tandon N, McIntosh RS, Elisei R, Ludgate M, Weetman AP 1994 T cell responses to orbital antigens in thyroid-associated ophthalmopathy. Clin Exp Immunol 96:329-334
262. Smith TJ, Bahn RS, Gorman CA 1989 Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr Rev 10:366-391
263. Trotter WR, Eden KC 1942 Localized pretibial myxoedema in association with toxic goitre. Q J Med 11:229-240
264. Watson EM, Pearce RH 1947 The mucopolysaccharide content of the skin in localized (pretibial) myxedema. Am J Clin Pathol 17:507-512
265. Smelser GK 1939 The histology of orbital and other fat tissue deposits in animals with experimentally produced exophthalmos. Am J Pathol 15:341-351
266. Wegelius O, Asboe-Hansen G, Lamberg B-A 1957 Retrobulbar connective tissue changes in malignant exophthalmos. Acta Endocrinologica 25:452-456
267. Paulson DL 1937 Experimental exophthalmos in the guinea pig. Proc Soc Exper Biol Med 36:604-609
268. Asboe-Hansen G, Iversen K 1951 Influence of thyrotrophic hormone on connective tissue. Pathogenetic significance of mucopolysaccharides in experimental exophthalmos. Acta Endocrinol 8:90-96
269. Ludwig AW, Boas NF, Soffer LI 1950 Role of mucopolysaccharides in pathogenesis of experimental exophthalmos. Proc Soc Exper Biol Med 73:137-146
270. Philipson LH, Schwartz NB 1984 Subcellular localization of hyaluronate synthetase in oligodendroglioma cells. J Biol Chem 259:5017-5023
271. Shyjan AM, Heldin P, Butcher EC, Yoshino T, Briskin MJ 1996 Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem 271:23395-23399
272. Watanabe K, Yamaguchi Y 1996 Molecular identification of a putative human hyaluronan synthase. J Biol Chem 271:22945-22948
273. Spicer AP, Olson JS, McDonald JA 1997 Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase. J Biol Chem 272:8957-8961
274. Spicer AP, Kaback LA, Smith TJ, Seldin MF 1998 Molecular cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes. J Biol Chem 273:25117-25124
275. Meyer K, Chaffee E, Hobby GL, Dawson MH 1941 Hyaluronidases of bacterial and animal origin. J Exp Med 73:309-326
276. Arbogast B, Hopwood JJ, Dorfman A 1975 Absence of hyaluronidase in cultured human skin fibroblasts. Biochem Biophys Res Commun 67:376-382
277. Smith TJ, Bahn RS, Gorman CA 1989 Hormonal regulation of hyaluronate synthesis in cultured human fibroblasts: evidence for differences between retroocular and dermal fibroblasts. J Clin Endocrinol Metab 69:1019-1023
278. Truppe W, Brasner R, von Figura K, Kresse H 1977 Uptake of hyaluronate by cultured cells. Biochem Biophys Res Commun 78:713-719
279. Noble PW, McKee CM, Cowman M, Shin HS 1996 Hyaluronan fragments activate an NF-κ B/I-κB α autoregulatory loop in murine macrophages. J Exp Med 183:2373-2378
280. Stamenkovic I, Amiot M, Pesando JM, Seed B 1989 A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell 56:1057-1062
281. Hall CL, Wang C, Lange LA, Turley EA 1994 Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity. J Cell Biol 126:575-588
282. Brecht M, Mayer U, Schlosser E, Prehm P 1986 Increased hyaluronate synthesis is required for fibroblast detachment and mitosis. Biochem J 239:445-450
283. Anderson RL, Tweeten JP, Patrinely JR, Garland PE, Thiese SM 1989 Dysthyroid optic neuropathy without extraocular muscle involvement. Ophthalmic Surg 20:568-574
284. Kazim M, Goldberg RA, Smith TJ 2002 Insights into the pathogenesis of thyroid associated orbitopathy. Arch Ophthalmol 120:380-386
285. Peyster RG, Ginsberg F, Silber JH, Adler LP 1986 Exophthalmos caused by excessive fat: CT volumetric analysis and differential diagnosis. AJNR 146:459-464
286. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM 1995 15-Deoxy-δ 12 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR γ. Cell 83:803-812
287. 2 metabolite binds peroxisome proliferator- activated receptor γ and promotes adipocyte differentiation. Cell 83:813-819
288. Kemp EG, Rootman J 1989 Lipid deposition within the extra-ocular muscles of a patient with dysthyroid ophthalmopathy. Orbit 8:45-48
289. Forster G, Otto E, Hansen C, Ochs K, Kahaly G 1998 Analysis of orbital T cells in thyroid-associated ophthalmopathy. Clin Exp Immunol 112:427-434
290. Pappa A, Calder V, Ajjan R, Fells P, Ludgate M, Weetman AP, Lightman S 1997 Analysis of extraocular muscle-infiltrating T cells in thyroid-associated ophthalmopathy (TAO). Clin Exp Immunol 109:362-369
291. Costagliola S, Many MC, Denef J-F, Pohlenz B, Reffetoff S, Vassart G 2000 Genetic immunization of outbred mice with thyrotropin receptor cDNA provides a model of Graves' disease. J Clin Invest 105:803-811
292. Smith RS, Smith TJ, Blieden TM, Phipps RP 1997 Fibroblasts as sentinel cells: synthesis of chemokines and regulation of inflammation. Am J Pathol 151:317-322
293. Fries KM, Blieden T, Looney RJ, Sempowski GD, Silvera MR, Willis RA, Phipps RP 1994 Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis. Clin Immunol Immunopathol 72:283-292
294. Morris RJ, Ritter MA 1980 Association of Thy-1 cell surface differentiation antigen with certain connective tissues in vivo. Cell Tissue Res 206:459-475
295. 3 on astrocytes and triggers formation of focal contact sites. Curr Biol 11:1028-1038
296. Phipps RP, Penney DP, Keng P, Quill H, Paxhia A, Derdak S, Felch ME 1989 Characterization of two major populations of lung fibroblasts: distinguishing morphology and discordant display of Thy 1 and class II MHC. Am J Respir Cell Mol Biol 1:65-74
297. - lung fibroblast subpopulations: enhancement of interleukin 1α production by tumor necrosis factor-α. Eur J Immunol 20:1723-1727
298. - lung fibroblast subpopulations. Am J Physiol 263:L283-L290
299. Fries KM, Felch ME, Phipps RP 1994 Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets. Am J Respir Cell Mol Biol 11:552-560
300. 2 synthesis of human orbital fibroblasts. Arthritis Rheum 28:315-322
301. Korn JH, Brinckerhoff CE, Edwards RL 1985 Synthesis of PGE2, collagenase and tissue factor substrains: substrains are differentially activated for different metabolic products. Coll Relat Res 5:437-447
302. 2 synthesis. J Clin Invest 71:1240-1246
303. Sisson JC, Spaugh BI, Vanderburg JA 1970 Functional aspects of fibroblasts derived from the retrobular tissue of man. Exp Eye Res 10:201-206
304. Sisson JC 1971 Stimulation of glucose utilization and glycosaminoglycans production by fibroblast derived from retrobulbar tissue. Exp Eye Res 12:285-292
305. Sisson JC, Vanderburg JA 1972 Lymphocyte-retrobulbar fibroblast interaction: mechanisms by which stimulation occurs and inhibition of stimulation. Invest Ophthalmol 11:15-20
306. Smith TJ 1984 Dexamethasone regulation of glycosaminoglycan synthesis in cultured human skin fibroblasts: similar effects of glucocorticoid and thyroid hormones. J Clin Invest 74:2157-2163
307. Smith TJ, Murata Y, Horwitz AL, Philipson L, Refetoff S 1982 Regulation of glycosaminoglycan synthesis by thyroid hormone in vitro. J Clin Invest 70:1066-1073
308. Henrikson RC, Smith TJ 1994 Ultrastructure of cultured human orbital fibroblasts. Cell Tissue Res 278:629-631
309. Smith TJ, Kottke RJ, Lum H, Andersen TT 1993 Human orbital fibroblasts in culture bind and respond to endothelin. Am J Physiol Cell Physiol 265:C138-C142
310. Berenson CS, Smith TJ 1995 Human orbital fibroblasts in culture express ganglioside profiles distinct from those in dermal fibroblasts. J Clin Endocrinol Metab 80:2668-2674
311. Smith TJ, Bahn RS, Gorman CA, Cheavens M 1991 Stimulation of glycosaminoglycan accumulation by interferon γ in cultured human retroocular fibroblasts. J Clin Endocrinol Metab 72:1169-1171
312. Young DA, Evans CH, Smith TJ 1998 Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions. Proc Natl Acad Sci USA 95:8904-8909
313. Smith TJ, Ahmed A, Hogg MG, Higgins PJ 1992 Interferon γ is an inducer of plasminogen activator inhibitor type-1 in human orbital fibroblasts. Am J Physiol Cell Physiol 263:C24-C29
314. Hogg MG, Evans CH, Smith TJ 1995 Leukoregulin induces plasminogen activator inhibitor type 1 in human orbital fibroblasts. Am J Physiol 269:C359-C366
315. Smith TJ, Sempowski GD, Wang HS, Del Vecchio PJ, Lippe SD, Phipps RP 1985 Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts. J Clin Endocrinol Metab 80:2620-2625
316. Smith TJ, Koumas L, Gagnow AM, Bell A, Sempowski GD, Phipps RP, Sorisky A 2002 Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 87:385-392
317. - subpopulations exhibit distinct phenotypes. Eur J Immunol 32:477-485
318. Uretsky SH, Kennerdell JS, Gutai JP 1980 Graves' ophthalmopathy in childhood and adolescence. Arch Ophthalmol 98:1963-1964
319. Wang HS, Cao HJ, Winn VD, Rezanka LJ, Frobert Y, Evans CH, Sciaky D, Young DA, Smith TJ 1996 Leukoregulin induction of prostaglandin-endoperoxide H synthase-2 in human orbital fibroblasts. An in vitro model for connective tissue inflammation. J Biol Chem 271:22718-22728
320. Cao HJ, Smith TJ 1999 Leukoregulin upregulation of prostaglandin endoperoxide H synthase-2 expression in human orbital fibroblasts. Am J Physiol 277:C1075-C1085
321. 2 synthase expression. J Biol Chem 277:16355-16364
322. 2 on murine helper-T-cell lymphokines. Immunomethods 2:255-260
323. 2 induces apoptosis in immature normal and malignant B lymphocytes. Clin Immunol Immunopathol 63:221-229
324. Hu ZQ, Asano K, Seki H, Shimamura T 1995 An essential role of prostaglandin E on mouse mast cell induction. J Immunol 155:2134-2142
325. Roper R, Phipps RP 1994 Regulation of the immune response by prostaglandin E2. Adv Prostaglandin Thromboxane Leukot Res 22:101-112
326. Cruikshank WW, Center DM, Nisar N, Wu M, Natke B, Theodore AC, Kornfeld H 1994 Molecular and functional analysis of a lymphocyte chemoattractant factor: association of biologic function with CD4 expression. Proc Natl Acad Sci USA 91:5109-5113
327. Zhang Y, Center DM, Wu DMH, Cruikshank WW, Yuan J, Andrews DW, Kornfeld H 1998 Processing and activation of prointerleukin-16 by caspace-3. J Biol Chem 273:1144-1149
328. Klimink PA, Goronzy JJ, Weyand CM 1999 IL-16 as an antiinflammatory cytokine in rheumatoid synovitis. J Immunol 162:4293-4299
329. Keates AC, Castagliuolo I, Cruikshank WW, Oui B, Arseneau KO, Brazer W, Kelly CP 2000 Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice. Gastroenterology 119:972-982
330. Sekigawa I, Matsushita M, Lee S, Maeda N, Ogasawara H, Kaneko H, Iida N, Hashimoto H 2001 A possible pathogenic role of CD8+ T cells and their derived cytokine, IL-16 in SLE. Autoimmunity 33:37-44
331. Schall TB, Bacon K, Toy KJ, Goeddel DV 1990 Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669-671
332. Wong M, Uddin S, Majchrzak B, Huynh T, Proudfoot AEI, Platanias LC, Fish EN 2001 RANTES activates Jak2 and Jak3 to regulate engagement of multiple signaling pathways in T cells. J Biol Chem 276:11427-11431
333. Simchen C, Lelumann I, Sittig D, Steiner M, Aust G 2000 Expression and regulation of regulated on activation, normal T cells expressed and secreted in thyroid tissue of patients with Graves' disease and thyroid autonomy and in thyroid-derived cell populations. J Clin Endocrinol Metab 85:4758-4762
334. Sciaky D, Brazer W, Center DM, Crukshank WW, Smith TJ 2000 Cultured human fibroblast express constitutive IL-16 mRNA: cytokine induction of active IL-16 protein synthesis through a caspace-3-dependent mechanism. J Immunol 164:3806-3814
335. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S 1994 The CD40 antigen and its ligand. Annu Rev Immunol 12:881-922
336. Noelle RJ, Roy M, Shepherd DM, Stamenkovic I, Ledbetter JA, Aruffo A 1992 A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci USA 89:6550-6554
337. Zhang Y, Cao HJ, Graf B, Meekins H, Smith TJ, Phipps RP 1998 Cutting edge: CD40 engagement up-regulates cyclooxygenase-2 expression and prostaglandin E2 production in human lung fibroblasts. J Immunol 160:1053-1057
338. Cao HJ, Wang HS, Zhang Y, Lin HY, Phipps RP, Smith TJ 1998 Activation of human orbital fibroblasts through CD40 engagement results in a dramatic induction of hyaluronan synthesis and prostaglandin endoperoxide H synthase-2 expression: insights into potential pathogenic mechanisms of thyroid-associated ophthalmopathy. J Biol Chem 273:29615-29625
339. Semposki GD, Rozenblit J, Samith TJ, Phipps RP 1998 Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production. Am J Physiol 274:C707-C714
340. Rotella CM, Zonefrati R, Toccafondi R, Valente WA, Kohn LD 1986 Ability to monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves' sera. J Clin Endocrinol Metab 62:357-367
341. Heufelder AE, Bahn RS 1992 Graves' immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts. Eur J Clin Invest 22:529-537
342. Pritchard J, Horst N, Cruikshank W, Smith TJ 2002 Igs from patients with Graves' disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol 168:942-950
343. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M 2000 Crystal structure of rhodopsin: AG protein-coupled receptor. Science 289:733-734
344. Dogan RE, Chenthamarakshan V, Holterman MJ, Prabhakar BS 2003 Absence of IL-4, and not suppression of Th2 response, prevents development of experimental autoimmune Graves' disease. J Immunol 170:2195-2204
345. Smith TJ 2002 Fibroblast biology in thyroid diseases. Curr Opin Endocrinol Diabetes 9:393-400