Immunoregulatory events in the skin of patients with cutaneous T-cell lymphoma

Archives of Dermatology

Volumn 132, Issue 5, 1996, Pages 554-561

  Hansen, Erik R ^a  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ADHESION MOLECULE; CYTOKINE;

ANTIGEN PRESENTATION; HUMAN; LANGERHANS CELL; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTIC INFILTRATION; MYCOSIS FUNGOIDES; PRIORITY JOURNAL; REVIEW; SEZARY SYNDROME; SKIN LYMPHOMA; T CELL LYMPHOMA; T LYMPHOCYTE ACTIVATION;

ANTIGEN-PRESENTING CELLS; CELL ADHESION MOLECULES; CHEMOTAXIS; CYTOKINES; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LYMPHOMA, T-CELL, CUTANEOUS; SKIN NEOPLASMS;

EID: 0029868620     PISSN: 0003987X     EISSN: None     Source Type: Journal    
DOI: 10.1001/archderm.132.5.554     Document Type: Review

References (107)

1. Weinstock MA, Horm JW. Mycosis fungoides in the United States: increasing incidence and descriptive epidemiology. JAMA. 1988;260:42-46.
2. Sterry W, Mielke V. CD4+ cutaneous T-cell lymphomas show the phenotype of helper/inducer Tcells (CD45RA-, CDw29+). J Invest Dermatol. 1989;93: 413-416.
3. Raltkiaer E, Wollt-Sneedorff A, Thomsen K, Geisler C, Vejlsgaard G. T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in the skin: a clinical, histological and immunophenotypic study. Exp Dermatol. 1992; 1:31-36.
4. Fujiwara Y, Abe Y, Kuyama M, et al. CD8+ cutaneous T-cell lymphoma with pagetoid epidermotropism and angiocentric and angiodestructive infiltration. Arch Dermatol. 1990;126:801-804.
5. Raltkiaer E. Immunohistological and genotypic studies of cutaneous malignant lymphomas compared with benign cutaneous conditions and cutaneous pseudolymphomas. Copenhagen, Denmark: University of Copenhagen; 1989. Thesis.
6. Slater DN. Cutaneous lymphoproliferative disorders: an assessment of recent investigative techniques. Br J Dermatol. 1991;124:309-323.
7. Ralfkiaer E, Wollf-Sneedorff A, Vejlsgaard G. Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas. Br J Dermatol. 1991;125:409-412.
8. Jensen JR, Thestrup-Pedersen K, Zachariae H, Sogaard H. Cyclosporin A therapy for mycosis fungoides. Arch Dermatol. 1987;123:160-163.
9. Thomsen K, Wantzin GL. Extracutaneous spreading with fatal outcome of mycosis fungoides in a patient treated with cyclosporin A: a word of caution. Dermatologica. 1987;174:236-238.
10. Crane GA, Variakojis D, Rosen ST, Sands AM, Roenigk HHJ. Cutaneous T-cell lymphoma in patients with human immunodeficiency virus infections. Arch Dermatol. 1991;127:989-994.
11. Penn I. Cancer in the immunosuppressed organ recipient. Transplant Proc. 1991;23:1771-1772.
12. Olsen EA, Delzell E, Jegasothy BV. Second malignancies in cutaneous T cell lymphoma. J Am Acad Dermatol. 1984;10:197-204.
13. MacKie RM. A monoclonal antibody technique to demonstrate an increase in Langerhans cells in cutaneous lesions of mycosis fungoides. Clin Exp Dermatol. 1982;7:43-47.
14. Fujita M, Horiguchi Y, Miyachi Y, Furukawa F, Kashihara-Sawami M, Imamura S. A subpopulation of Langerhans cells (CD1a+Lag-) increased in the dermis of plaque lesions of mycosis fungoides. J Am Acad Dermatol. 1991;25: 491-499.
15. Lisby S, Baadsgaard O, Cooper KD, Thomsen K, Wantzin GR. Expression of OKM5 antigen on epidermal cells in mycosis fungoides plaque stage. J Invest Dermatol. 1988;90:716-719.
16. Hansen ER, Baadsgaard O, Lisby S, Cooper KD, Thomsen K, Vejlsgaard GL. Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+ OKM5- antigen-presenting cells. J Invest Dermatol. 1990;94:485-491.
17. Lisby S, Baadsgaard O, Cooper K, et al. Phenotype, ultrastructure, and function of CD1+ DR+ epidermal cells that express CD36 (OKM5) in cutaneous T-cell lymphoma. Scand J Immunol. 1990;32:111-120.
18. Ralfkiaer E, Stein H, Bosq J, et al. Expression of a cell-cycle-associated nuclear antigen (Ki-67) in cutaneous lymphoid infiltrates. Am J Dermatopathol. 1986; 8:37-43.
19. Chadburn A, Inghirami G, Knowles DM. T-cell activation-associated antigen expression by neoplastic T-cells. Hematol Pathol. 1992;6:131-141.
20. Berger CL, Morrison S, Chu A, et al. Diagnosis of cutaneous T cell lymphoma by use of monoclonal antibodies reactive with tumor-associated antigens. J Clin Invest. 1982;70:1205-1215.
21. Sterry W, Pullmann H, Steigleder GK. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas. Arch Dermatol Res. 1981;270: 285-290.
22. Depper JM, Leonard WJ, Kronke M, Waldmann TA, Greene WC. Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol. 1984;133:1691-1695.
23. Waldmann TA. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986;232:727-732.
24. Oishi M, Johno M, Ono T, Honda M. Differences in IL-2 receptor levels between mycosis fungoides and cutaneous type adult T-cell leukemia/lymphoma in the early stages of the disease. J Invest Dermatol. 1994;102: 710-715.
25. Cooper K, Meunier L, Ho V, et al. Activation of reactive versus malignant T cells in cutaneous T cell lymphoma: role of abnormal antigen presenting cells and T cell activating molecules. In: Lambert WC, ed. Basic Mechanisms of Physiological and Aberrant Lymphoproliferation in the Skin. New York. NY: Plenum Press; 1994.
26. Taylor RS, Baadsgaard O, Hammerberg C, Cooper KD. Hyperstimulatory CD1a+CD1b+CD36+ Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesional epidermal cells of patients with atopic dermatitis. J Immunol. 1991;147:3794-3802.
27. Walsh LJ, Seymour GJ, Powell RN. Modulation of class II (DR and DQ) antigen expression on gingival Langerhans cells in vitro by gamma interferon and prostaglandin E2. J Oral Pathol. 1986;15:347-351.
28. Hansen E, Bang B, Larsen K, Vejlsgaard G, Baadsgaard O. In cutaneous T-cell lymphoma, class II MHC molecules on CD1+ antigen presenting cells are upregulated in involved compared to uninvolved epidermis. Br J Dermatol. 1994;131:780-788.
29. Tan RS, Butterworth CM, McLaughlin H, Malka S, Samman PD. Mycosis fungoides: a disease of antigen persistence. Br J Dermatol. 1974;91:607-616.
30. Tosca A, Linardopoulos S, Malliri A, Hatziolou E, Nicolaidou A, Spandidos DA. Implication of the ras and myc oncoproteins in the pathogenesis of mycosis fungoides. Anticancer Res. 1991;11:1433-1438.
31. Popovic M. Reitz MSJ, Sarngadharan MG, et al. The virus of Japanese adult T-cell leukaemia is a member of the human T-cell leukaemia virus group. Nature. 1982;300:63-66.
32. Wanzin GL, Thomsen K, Nissen NI, Saxinger C, Gallo RC. Occurrence of human T cell lymphotropic virus (type I) antibodies in cutaneous T cell lymphoma. J Am Acad Dermatol. 1986;15:598-602.
33. van der Loo EM, van Muijen GN, van Vloten WA, Beens W, Scheffer E, Meijer CJ. C-type virus-like particles specifically localized in Langerhans cells and related cells of skin and lymph nodes of patients with mycosis fungoides and Sezary's syndrome: a morphological and biochemical study. Virchows Arch B Cell Pathol. 1979;31:193-203.
34. Whittaker SJ, Luzzatto L. HTLV-1 provirus and mycosis fungoides. Science. 1993;259:1470.
35. Ho V, Baadsgaard O, Elder J, et al. Genotypic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor infiltrating lymphocytes. J Invest Dermatol. 1990;95:4-8.
36. Charley M, McCoy JP, Deng JS, Jegasothy B. Anti-V region antibodies as almost clonotypic reagents for the study of cutaneous T cell lymphomas and leukemias. J Invest Dermatol. 1990;95:614-617.
37. Tokura Y, Heald PW, Van SL, Edelson RL. Stimulation of cutaneous T-cell lymphoma cells with superantigenic staphylococcal toxins. J Invest Dermatol. 1992;98:33-37.
38. Tokura Y, Yagi H, Ohshima A, et al. Cutaneous colonization with staphylococci influences the disease activity of Sezary syndrome: a potential role for bacterial superantigens. Br J Dermatol. 1995;133:6-12.
39. Higgs JB, Zeldes W, Kozarsky K, et al. A novel pathway of human T lymphocyte activation: identification by a monoclonal antibody generated against a rheumatoid synovial T cell line. J Immunol. 1988;140:3758-3765.
40. Meuer SC, Hussey RE, Fabbi M, et al. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984;36:897-906.
41. Jenkins MK, Taylor PS, Norton SD, Urdahl KB. CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells. J Immunol. 1991;147:2461-2466.
42. Selvaraj P, Plunkett ML, Dustin M, Sanders ME, Shaw S, Springer TA. The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. Nature. 1987;326:400-403.
43. Linsley PS, Clark EA, Ledbetter JA. T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990;87:5031-5035.
44. De Panfilis G, Manara GC, Ferrari C, Torresani C. Adhesion molecules on the plasma membrane of epidermal cells, III: keratinocytes and Langerhans cells constitutively express the lymphocyte function-associated antigen 3. J Invest Dermatol. 1991;96:512-517.
45. Lee MG, Borkowski TA, Udey MC. Regulation of expression of B7 by murine Langerhans cells: a direct relationship between B7 rnRNA levels and the level of surface expression of B7 by Langerhans cells. J Invest Dermatol. 1993: 101:883-886.
46. Simon J, Dietrich A, Mielke V, et al. Distribution of the B7 activation antigen and its ligand CD28 in T cell mediated skin diseases. J Invest Dermatol. 1993; 100:576. Abstract.
47. Kniep B, Flegel WA, Northoff H, Rieber EP. CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution. Blood. 1993;82:1776-1786.
48. Springer TA. Adhesion receptors of the immune system. Nature. 1990;346: 425-434.
49. Hansen E, Vejlsgaard G, Cooper K, et al. Leukemic T cells from patients with cutaneous T-cell lymphoma demonstrate enhanced activation through CDw60, CD2, and CD28 relative to activation through the T-cell antigen receptor complex. J Invest Dermatol. 1993;100:667-673.
50. Kaltoft K, Bisballe S, Dyrberg T, Boel E, Rasmussen PB, Thestrup-Pedersen K. Establishment of two continuous T-cell strains from a single plaque of a patient with mycosis fungoides. In Vitro Cell Dev Biol. 1992;28A:161-167.
51. Kaltoft K, Bisballe S, Rasmussen HF, Thestrup-Pedersen K, Thomsen K, Sterry W. A continuous T-cell line from a patient with Sezary syndrome. Arch Dermatol Res. 1987;279:293-298.
52. Kaltoft K, Thestrup-Pedersen K, Jensen JR, Bisballe S, Zachariae H. Establishment of T and B cell lines from patients with mycosis fungoides. Br J Dermatol. 1984;111:303-308.
53. Gazdar AF, Carney DN, Bunn PA, et al. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980;55:409-417.
54. Braylan R, Variakojis D, Yachnin S. The Sezary syndrome lymphoid cell: abnormal surface properties and mitogen responsiveness. Br J Haematol. 1975; 31:553-564.
55. Burg G, Rodt H, Grosse-Wilde H, Braun-Falco O. Surface markers and mitogen response of cells harvested from cutaneous infiltrates in mycosis fungoides and Sézary's syndrome. J Invest Dermatol. 1978;70:257-259.
56. Abrams JT, Lessin SR, Ghosh SK, et al. Malignant and nonmalignant T cell lines from human T cell lymphotropic virus type I-negative patients with Sézary syndrome. J Immunol. 1991;146:1455-1462.
57. Abrams JT, Lessin S, Ghosh SK, et al. A clonal CD4-positive T-cell line established from the blood of a patient with Sézary syndrome. J Invest Dermatol. 1991;96:31-37.
58. Boehncke WH, Gerdes J, Wiese M, Kaltoft K, Sterry W. A majority of proliferating T cells in cutaneous malignant T cell lymphomas may lack the high affinity IL-2 receptor (CD25). Arch Dermatol Res. 1993;285:127-130.
59. Starkebaum G, Loughran TPJ, Waters CA, Ruscetti FW. Establishment of an IL-2 independent, human T-cell line possessing only the p70 IL-2 receptor. Int J Cancer. 1991;49:246-253.
60. Yodoi J, Uchiyama T. Diseases associated with HTLV-I: virus, IL-2 receptor dysregulation and redox regulation. Immunol Today. 1992;13:405-411.
61. Dalloul A, Laroche L, Bagot M, et al. Interleukin-7 is a growth factor for Sézary lymphoma cells. J Clin Invest. 1992;90:1054-1060.
62. Foss F, Koc Y, Stetler-Stevenson M. Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: potential autocrine or paracrine effectors in the Sézary syndrome. J Clin Oncol. 1994;12:326-335.
63. Frishman J, Long B, Knospe W, Gregory S, Plate J. Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia. J Exp Med. 1993;177:955-964.
64. Rich B, Campos-Torres J, Tepper R, Moreadith R, Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med. 1993;177:305-316.
65. Iron VA, Rosenthal D, Sauder DN. Epidermal interleukin-1 is increased in cutaneous T-cell lymphoma. J Invest Dermatol. 1988;90:378-381.
66. Hansen ER, Vejlsgaard GL, Lisby S, Heldenheim M, Baadsgaard O. Epidermal interleukin 1 alpha functional activity and interleukin 8 immunoreactivity are increased in patients with cutaneous T-cell lymphoma. J Invest Dermatol. 1991;97:818-823.
67. Dowd P, Hudspith B, Miller J. Release in vivo of interleukin-1 (IL-1) like activity by human skin. Clin Exp Immunol. 1987;67:606-610.
68. Zachariae C, Larsen CS, Kaltoft K, Deleuran B, Larsen CG, Thestrup-Pedersen K. Soluble IL2 receptor serum levels and epidermal cytokines in mycosis fungoides and related disorders. Acta Derm Venereol Stockh. 1991; 71:465-470.
69. Lawlor F, Smith NP, Camp RD, et al. Skin exudate levels of interleukin 6, Interleukin 1 and other cytokines in mycosis fungoides. Br J Dermatol. 1990; 123:297-304.
70. Braverman I, Johnson C. Epidermal interleukin 1 alpha bioactivity is depressed in lesional skin of mycosis fungoides patients because of overutilization. J Invest Dermatol. 1993;100:570. Abstract.
71. Miossec P, Yu CL, Ziff M. Lymphocyte chemotactic activity of human interleukin 1. J Immunol. 1984;133:2007-2011.
72. Sica A, Matsushima K, Van Damme J, et al. IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-B gene in endothelial cells. Immunology. 1990;69:548-553.
73. Zachariae C, Jinquan T, Nielsen V, Kaltoft K, Thestrup-Pedersen K. Phenotypic determination of T-lymphocytes responding to chemotactic stimulation from fMLP, IL-8, human IL-10, and epidermal lymphocyte chemotactic factor. Arch Dermatol Res. 1992;284:333-338.
74. Wismer J, McKencie R, Sauder D. Interleukin-8 immunoreactivity in epidermis of cutaneous T-cell lymphoma patients. Lymphokine Cytokine Res. 1994; 13:21-27.
75. Sarris A, Esgleyes T, Crow M, et al. Cytokine loops involving interferon-gamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma? J Am Soc Hematol. 1995;86:651-658.
76. Ishii T, Walsh LJ, Seymour GJ, Powell RN. Modulation of Langerhans cell surface antigen expression by recombinant cytokines. J Oral Pathol Med. 1990; 19:355-359.
77. Walsh LJ, Parry A, Scholes A, Seymour GJ. Modulation of CD4 antigen expression on human gingival Langerhans cells by gamma Interferon. Clin Exp Immunol. 1987;70:379-385.
78. Berman B, Duncan MR, Smith B, Ziboh VA, Palladino M. Interferon enhancement of HLA-DR antigen expression on epidermal Langerhans cells. J Invest Dermatol. 1985;84:54-58.
79. Barker JN, Allen MH, MacDonald DM. The effect of in vivo interferon gamma on the distribution of LFA-1 and ICAM-1 in normal human skin. J Invest Dermatol. 1989;93:439-442.
80. Wayner E, Hoffstrom B, Pittlekow M. T Lymphocyte adhesion to keratinocytes: cooperative role for the integrin receptor alpha 3 beta 1 and E-cadherin. J Invest Dermatol. 1994;102:524. Abstract.
81. Sterry W, Mielke V, Konter U, Kellner I, Boehncke WH. Role of beta 1-integrins in epidermotropism of malignant T cells. Am J Pathol. 1992;141:855-860.
82. Picker LJ, Michie SA, Rott LS, Butcher EC. A unique phenotype of skin-associated lymphocytes in humans: preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990;136:1053-1068.
83. Vejlsgaard GL, Ralfkiaer E, Avnstorp C, Czajkowski M, Marlin SD, Rothlein R. Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomas. J Am Acad Dermatol. 1989;20:782-790.
84. Nickoloff BJ, Griffiths CE, Baadsgaard O, Voorhees JJ, Hanson CA, Cooper KD. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome. JAMA. 1989;261:2217-2221.
85. Ansel J, Perry P, Brown J, et al. Cytokine modulation of keratinocyte cytokines. J Invest Dermatol. 1990;94:101S-107S.
86. Salgame P, Abrams JS, Clayberger C, et al. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991;254: 279-282.
87. Powrie F, Coffman RL. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today. 1993;14:270-274.
88. Saed G, Fivenson DP, Naidu Y, Nickoloff B. Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sézary syndrome expresses a Th2-type profile. J Invest Dermatol. 1994;103:29-33.
89. Vowels BR, Cassin M, Vonderheid EC, Rook AH. Aberrant cytokine production by Sézary syndrome patients: cytokine secretion pattern resembles murine Th2 cells. J Invest Dermatol. 1992;99:90-94.
90. Vowels B, Lessin S, Cassin C, et al. Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma. J Invest Dermatol. 1994;103:669-673.
91. Rook A, Lessin S, Jaworsky C, Singh A, Vowels B. The immunopathogenesis of cutaneous T-cell lymphoma: abnormal cytokine production by Sézary T-cells. Arch Dermatol. 1993;129:486-489.
92. Reinhold U, Abken H, Kukel S, et al. Tumor-infiltrating lymphocytes isolated from a Ki-1-positive large cell lymphoma of the skin: phenotypic characterization and analysis of cytokine secretion. Cancer. 1991;68:2155-2160.
93. Wood NL, Kitces EN, Blaylock WK. Depressed lymphokine activated killer cell activity in mycosis fungoides: a possible marker for aggressive disease. Arch Dermatol. 1990;126:907-913.
94. D'Andrea A, Aste-Amezaga M, Valiante X, Ma M, Trinchieri K. Trinchieri G. Interleukin 10 inhibits human lymphocyte IFN-gamma production by suppressing natural killer cells stimulatory factor/interleukin-12 synthesis in accessory cells. J Exp Med. 1993;178:1041.
95. Meissner K, Loning T, Rehpenning W. Epidermal Langerhans cells and prognosis of patients with mycosis fungoides and Sézary syndrome. In Vivo. 1993; 7:277-280.
96. Hoppe R, Medeiros L, Warnke R, Wood G. CD8+ tumor infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. J Am Acad Dermatol. 1995;32:448-453.
97. Salmeron A, Morita T, Seki H, Platsoucas C, Itoh K. Lymphokine production by human melanoma tumor infiltrating lymphocytes. Cancer Immunol Immunother. 1992;35:211-217.
98. Reinhold U, Pawelec G, Fratila A, Leippold S, Bauer R, Kreysel HW. Phenotypic and functional characterization of tumor infiltrating lymphocytes in mycosis fungoides: continuous growth of CD4+ CD45R+ T-cell clones with suppressor-inducer activity. J Invest Dermatol. 1990;94:304-309.
99. Fivenson D, Nickoloff B. Cell trafficking networks in cutaneous T cell lymphoma: In: Lambert WE, ed. Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin. New York, NY: Plenum Press; 1994:77-93.
100. Bergstresser P, Sullivan S, Streilein J, Tigelaar R. Origin and fuction of Thy-1+ dendritic epidermal cells in mice. J Invest Dermatol. 1985;85:85s-90s.
101. Kaplan EH, Rosen ST, Norris DB, Roenigk HHJ, Saks SR, Bunn PAJ. Phase II study of recombinant human Interferon gamma for treatment of cutaneous T-cell lymphoma. J Natl Cancer Inst. 1990;82:208-212.
102. Vowels BR, Cassin M, Boufal MH, Walsh LJ, Rook AH. Extracorporeal photochemotherapy induces the production of tumor necrosis factor-alpha by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis. J Invest Dermatol. 1992;98:686-692.
103. Marolleau J, Baccard M, Flageul B, et al. High-dose recombinant interleukin-2 in advanced cutaneous T-cell lymphoma. Arch Dermatol. 1995;132: 574-579.
104. Nagatani T, Kin ST, Baba N, Miyamoto H, Nakajima H, Katoh Y. A case of cutaneous T cell lymphoma treated with recombinant interleukin 2 (rIL-2). Acta Derm Venereol Stockh. 1988;68:504-508.
105. Kruse N, Tony HP, Sebald W. Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement. EMBO J. 1992;11: 3237-3244.
106. Trinchieri G. Interleukin-12 and its role in the generation of TH1 cells. Immunol Today. 1993;14:335-338.
107. Rook A, Kubin M, Cassin M. IL-12 reverses cytokine and immune abnormalities in Sézary syndrome. J Immunol. 1995;154:1491-1498.