Cellular and biochemical requirements for thymocyte negative selection

Seminars in Immunology

Volumn 8, Issue 2, 1996, Pages 69-82

  Page, Dawne M ^a   Kane, Lawrence P ^a   Onami, Thandi M ^a   Hedrick, Stephen M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Apoptosis; Calcium; Co receptor; Kinase; Thymocyte

Indexed keywords

AUTOANTIGEN;

ANTIGEN PRESENTING CELL; ANTIGEN RECOGNITION; APOPTOSIS; CELL MATURATION; LYMPHOCYTE DIFFERENTIATION; REVIEW; T LYMPHOCYTE; THYMOCYTE;

EID: 0029918798     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1006/smim.1996.0010     Document Type: Review

References (140)

1. Robey E, Fowlkes BJ (1994) Selective events in T cell development. Annu Rev Immunol 12:675-705
2. Kappler JW, Staerz U, White J, Marrack PC (1988) Self-tolerance eliminates T cells specific for MIs-modified products of the major histocompatibility complex. Nature 332:35-40
3. Kisielow P, Bluthmann H, Staerz UD, Steinmetz M, von Boehmer H (1988) Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes Nature 333:742-746
4. Sha WC, Nelson CA, Newberry RD, Kranz DM, Russell JH, Loh DY (1988) Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 336:73-76
5. Kaye H, Hsu ML, Sauron ME, Jameson SC, Gascoigne NR, Hedrick SM (1989) Selective development of CDR+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 341:746-749
6. Pircher H, Burki K, Lang R, Hengartner H, Zinkernagel RM (1989) Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342:559-561
7. Morishima C, Norby-Slycord C, McConnell KR, Finch RJ, Nelson AJ, Farr AG, Pullen AM (1994) Expression of two structurally identical viral superantigens results in thymic elimination at distinct developmental stages. J Immunol 153:5091-5103
8. Swat W, Ignatowicz L, von Boehmer H, Kisielow P (1991) Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells. Nature 351:150-153
9. Vasquez NJ, Kaye J, Hedrick SM (1992) In vivo and vitro clonal deletion of double-positive thymocytes J Exp Med 175:1307-1316
10. Carlow DA, van Oers NS, Teh SJ, Teh HS (1992) Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. J Immunol 148:1595-1603
11. Iwabuchi K, Nakayama K, McCoy RL, Wang F, Nishimura T, Habu S, Murphy KM, Loh DY (1992) Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes. Proc Natl Acad Sci USA 89:9000-9004
12. Spain LM, Berg LJ (1992) Developmental regulation of thymocyte susceptibility to deletion by 'self-peptide. J Exp Med 176:213-223
13. Tanaka Y, Mamalaki C, Stockinger B, Kioussis D (1993) In vitro negative selection of alpha beta T cell receptor transgenic thymocytes by conditionally immortalized thymic cortical epithelial cell lines and dendritic cells. Eur J Immunol 23:2614-2621
14. Aiba Y, Mazda O, Davis MM, Muramatsu S, Katsura Y (1994) Requirement of a second signal from antigen presenting cells in the clonal deletion of immature T cells. Int Immunol 6:1475-1483
15. Page DM, Kane LP, Allison JP, Hedrick SM (1993) Two signals are required for negative selection of CD4+CD8+ thymocytes. J Immunol 151:1868-1880
16. 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
17. Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349-1356
18. Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356:607-609
19. Gimmi CD, Freeman GJ, Gribben JG, Gray G, Nadler LM (1993) Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci USA 90:6586-6590
20. Strasser A (1995) Apoptosis. Death of a T cell [news; comment]. Nature 373:385-386
21. Nakashima I, Zhang YH, Rahman SM, Yoshida T, Isobe K, Ding LN, Iwamoto T, Hamaguchi M, Ikezawa H, Taguchi R (1991) Evidence of synergy between Thy-1 and CD3/TCR complex in signal delivery to murine thymocytes for cell death. J Immunol 147:1153-1162
22. Kearse KP, Takahama Y, Punt JA, Sharrow SO, Stringer A (1995) Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection. J Exp Med 181:193-202
23. Kersh GJ, Hedrick SM (1995) Role of TCR specificity in CD4 versus CD8 lineage commitment. J Immunol 154:1057-1068
24. Gross JA, Callas E, Allison JP (1992) Identification and distribution of the costimulatory receptor CD28 in the mouse. J Immunol 149:380-388
25. Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattel MG, Golstein P (1987) A new member of the immunoglobulin super family - CTLA-4 Nature 328:267-270
26. Degermann S, Surh CD, Glimcher LH, Sprent J, Lo D (1994) B7 expression on thymic medullary epithelium correlates with epithelium-mediated deletion of V beta 5+ thymocytes. J Immunol 152:325-43263
27. Razi-Wolf Z, Freeman GJ, Galvin F, Benacerraf B, Nadler L, Reiser H (1992) Expression and function of the murine B7 antigen, the major costimulatory molecule expressed by peritoneal exudate cells. Proc Natl Acad Sci USA 89:4210-4214
28. Razi-Wolf Z, Falo LDJ, Reiser H (1994) Expression and function of the costimulatory molecule B7 on murine Langerhans cells: evidence for an alternative CTLA-4 ligand. Eur J Immunol 24:805-811
29. Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, Banchereau J(1994) B70/ B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med 180:1841-1847
30. Jones LA, Izon DJ, Nieland JD, Linsley PS, Kruisbeek AM (1994) CD28-B7 interactions are not required for intrathymic clonal deletion. J Immunol 152:3254-3263
31. Shahinian A, Pfeffer K, Lee KP, Kundig TM, Kishihara K, Wakeham A, Kawai K, Ohashi PS, Thompson CB, Mak TW (1994) Differential T cell costimulatory requirements in CD28-deficient mice. J Immunol 152:3254-3263
32. Tan R, Teh SJ, Ledetter JA, Linsley PS, Teh HS (1992) B7 costimulates proliferation of CD4-8+ T lymphocytes but is not required for the deletion of immature CD4+8+ thymocytes. J Immunol 149:3217-3224
33. Punt JA, Osborne BA, Takahama Y, Sharrow SO, Singer A (1994) Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J Exp Med 179:709-713
34. Bierer BE, Peterson A, Gorga JC, Herrmann SH, Burakoff SJ (1988) Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor. J Exp Med 168:1145-1156
35. Van Seventer GA, Shimizu Y, Morgan KJ, Shaw S (1990) The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 144:4579-4586
36. van Seventer GA, Newman W, Shimizu Y, Nutman TB, Tanaka Y, Horgan KJ, Gopal TV, Ennis E, O'Sullivan D, Grey H, et al (1991) Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med 174:901-913
37. Damle NK, Aruffo A (1991) Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+ T lymphocytes. Proc Natl Acad Sci USA 88:6403-6407
38. Liu Y, Jones B, Aruffo A, Sullivan KM, Linsley PS, Janeway CAJ (1992) Heat-stable antigen is a costimulatory molecule for CD4 T cell growth. J Exp Med 175:437-445
39. Killeen N, Stuart SG, Littman DR (1994) Development and function of T cells in mice with a disrupted CD2 gene. J Immunol 152:3254-3263
40. Green JM, Zheng XG, Shimizu Y, Thompson CB, Turka LA (1994) T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA-1-mediated events. Eur J Immunol 24:265-272
41. 2+ levels. J Immunol 149:3872-3880
42. Boussiotis VA, Freeman GJ, Gray G, Gribben J, Nadler LM (1992) B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance. J Immunol 149:380-388
43. Xu H, Gonzalo JA, St Pierre Y, Williams IR, Kupper TS, Cotran RS, Springer TA, Gutierrez-Ramos JC (1994) Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J Exp Med 180:95-109
44. Sligh JEJ, Ballantyne CM, Rich SS, Hawkins HK, Smith CW, Bradley A, Beaudet AL (1993) Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc Natl Acad Sci USA 90:8529-8533
45. Hough MR, Takei F, Humphries RK, Kay R (1994) Defective development of thymocytes overexpressing the costimulatory molecule, heat-stable antigen. J Exp Med 179:177-184
46. Drappa J, Brot N, Elkon KB (1993) The Fas protein is expressed at high levels on CD4+CD8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, MRL lpr/lpr. Proc Natl Acad Sci USA 90:10340-10344
47. 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. Proc Natl Acad Sci USA 90:8529-8533
48. Kotzin BL, Babcock SK, Herron LR (1988) Deletion of potentially self-reactive T cell receptor specificities in L3T4-, Lyt-2-T cells of lpr mice [published erratum appears in J Exp Med 1989 Apr 1; 169(4):1515-6]. J Exp Med 168:2221-2229
49. Singer PA, Balderas RS, McEvilly RJ, Bobardt M, Theofilopoulos AN (1989) Tolerance-related V beta clonal deletionsin normal CD4-8-, TCR-alpha/ beta + and abnormal lpr and gld cell populations. J Exp Med 170:1869-1877
50. Sidman CL, Marshall JD, Von Boehmer H (1992) Transgenic T cell receptor interactions in the lymphoproliferative and autoimmune syndromes of lpr and gld mutant mice. Eur J Immunol 22:499-504
51. Singer GG, Abbas AK (1994) The fas antigen is involved in peripheral but not thymic deletion of T lymphocytesin T cell receptor transgenic mice. Immunity 1:365-371
52. Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins activation, costimulation, and death. Cell 76:959-962
53. Cowan WK, Sorensen GD (1964) Electron microscopic observations of acute thymic involution produced by hydrocortisone. Lab Invest 13:353
54. Duijvestijn AM, Hoefsmit EC (1981) Ultrastructure of the rat thymus: the micro-environment of T-lymphocyte maturation. Cell Tissue Res 218:279-292
55. Kendall MD (1990) The cell biology of cell death in the thymus. Thymus Update 53-76
56. Surh CD, Sprent J (1994) T-cell apoptosis detected in situ during positive and negative selection in the thymus [see comments]. Nature 372:100-103
57. Le PT, Maecker HT, Cook JE (1995) In situ detection and characterization of apoptotic thymocytes in human thymus Expression of bcl-2 in vivo does not prevent apoptoss. J Immunol 154:4371-4378
58. Matzinger P, Guerder S (1989) Does T-cell tolerance require a dedicated antigen-presenting cell? Nature 338:74-76
59. Mazda O, Watanabe Y, Gyotoku J, Katsura Y (1991) Requirement of dendritic cells and B cells in the clonal deletion of MIs-reactive T cells in the thymus. J Exp Med 173:539-547
60. Miyazaki T, Suzuki G, Yamamura K (1993) The role of macrophages in antigen presentation and T cell tolerance. Int Immunol 5:1023-1033
61. Barclay AN, Mayrhofer G (1981) Bone marrow origin of Ia-positive cells in the medulla rat thymus. Cell Tissue Res 218:279-292
62. Beller DI, Unanue ER (1993) IA antigens and antigen-presenting function of thymic macrophages. Proc Natl Acad Sci USA 90:6586-6590
63. Foy TM, Durie FH, Noelle RJ (1994) The expansive role of CD40 and its ligand, gp39, in immunity. Semin Immunol 6:259-266
64. Foy TM, Page DM, Waldschmidt TJ, Schoneveld A, Laman JD, Masters SR, Tygrett L, Ledbetter JA, Aruffo A, Claassen E, Xu JC, Flavell RA, Oehen S, Hedrick SM, Noelle RJ (1995) An essential role for gp39, the ligand for CD40, in thymic selection. J Exp Med 182:1377-1388
65. Notarangelo LD, Duse M, Ugazio AG (1993) Immunodeficiency with hyper-IgM (HIM). Proc Natl Acad Sci USA 90:6586-6590
66. Chervonsky AV, Xu J, Barlow AK, Khery M, Flavell RA, Janeway CAJ (1995) Direct physical interaction involving CD40 ligand on T cells and CD40 on B cells is required to propagate MMTV. Immunity 3:139-146
67. Galy AH, Spits H (1992) CD40 is functionally expressed on human thymic epithelial cells. J Immunol 149:775-782
68. Ranheim EA, Kipps TJ (1993) Activated T cells induce expression of B7/ BB1 on normal or leukemic B cells through a CD40-dependent signal. J Exp Med 177:925-935
69. Kennedy MK, Mohler KM, Shanebeck KD, Baum PR, Picha KS, Otten-Evans CA, Janeway CAJ, Grabstein KH (1994) Induction of B cell costimulatory function by recombinant murine CD40 ligand. Eur J Immunol 24:116-123
70. Roy M, Aruffo A, Ledbetter J, Linsley P, Kehry M, Noelle R (1993) Studies on the interdependence of gp39 and B7 expression and function during antigen-specific immune responses. Proc Natl Acad Sci USA 90:8529-8533
71. McConkey DJ, Nicotera P, Orrenius S (1994) Signalling and chromatin fragmentation in thymocyte apoptosis. Immunol Rev 142:343363
72. McConkey DJ, Fosdick L, D'Adamio L, Jondal M, Orrenius S (1994) Co-receptor (CD4/ CD8) engagement enhances CD3-induced apoptosis in thymocytes. Implications for negative selection. J Immunol 153:2436-2443
73. McConkey DJ, Jondal M, Orrenius S (1992) Cellular signaling in thymocyte apoptosis. Semin Immunol 4:371-377
74. Cohen JJ (1992) Glucocorticoid-induced apoptosis in the thymus. Semin Immunol 4:363-369
75. Cohen JJ, Duke RC, Fadok VA, Sellins KS (1992) Apoptosis and programmed cell death in immunity. Annu Rev Immunol 10:267-293
76. Weiss A, Littman DR (1994) Signal transduction by lymphocyte antigen receptors. Cell 76:263-274
77. Rothenberg EV (1994) Signaling mechanisms in thymocyte selection. Curr Opin Immunol 6:257-265
78. Pfeffer K, Mak TW (1994) Lymphocyte ontogeny and activation in gene targeted mutant mice. Annu Rev Immunol 12:367-411
79. lck. Nature 357:161-164
80. lck in thymopoiesis. EMBO J 12:1671-1680
81. lck in the antigen-stimulated clonal deletion of thymocytes. Science 257:94-96
82. Cooke MP, Abraham KM, Forbush KA, Perlmutter RM (1991) Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell 65:281-291
83. fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell 70:741-750
84. Guidos CJ, Danska JS, Fathman CG, Weissman IL (1990) T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages. J Exp Med 172:835-845
85. Chan AC, van Oers NS, Tran A, Turka L, Law CL, Ryan JC, Clark EA, Weiss A (1994) Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol 152:4758-4766
86. Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM (1994) Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell 76:947-958
87. Elder ME, Lin D, Clever J, Chan AC, Hope TJ, Weiss A, Parslow TG (1994) Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science 264:1596-1599
88. Chan AC, Kadlecek TA, Elder ME, Filipovich AH, Kuo WL, Iwashima M, Parslow TG, Weiss A (1994) ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science 264:1599-1601
89. Negishi I, Motoyama N, Nakayama K-I, Nakayama K, Senju S, Hatakeyama S, Zhang Q, Chan AC, Loh DY (1995) Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376:435-438
90. Janeway CAJ (1992) The T cell receptor asa multicomponent signalling machine: CD4/ CD3 coreceptors and CD45 in T cell activation. Annu Rev Immunol 10:645-674
91. Koretzky GA, Picus J, Schultz T, Weiss A (1991) Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production. Proc Natl Acad Sci USA 88:2037-2041
92. Koretzky GA, Picus J, Thomas ML, Weiss A (1990) Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature 346:66-68
93. Mustelin T, Coggeshall KM, Altman A (1989) Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase. Proc Natl Acad Sci USA 86:6302-6306
94. Ostergaard HL, Shackelford DA, Hurley TR, Johnson P, Hyman R, Sefton BM, Trowbridge IS (1989) Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T-cell lines. Proc Natl Acad Sci USA 86:8959-8963
95. Hurley TR, Hyman R, Sefton BM (1993) Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn, and c-src tyrosine protein kinases. Mol Cell Biol 13:1651-1656
96. McFarland ED, Hurley TR, Pingel JT, Sefton BM, Shaw A, Thomas ML (1993) Correlation between Src family member regulation by the protein-tyrosine-phosphatase CD45 and transmembrane signaling through the T-cell receptor. Proc Natl Acad Sci USA 90:1402-1406
97. Kishihara K, Penninger J, Wallace VA, Kundig TM, Kawai K, Wakeham A, Timms E, Pfeffer K, Ohashi PS, Thomas ML, Furlonger C, Paige CJ, Mak TW (1993) Normal B lymphocyte development but impaired T cell maturation in CD45-Exon6 protein tyrosine phosphatase-deficient mice. Cell 74:143-156
98. Ong CJ, Chui D, Teh HS, Marth JD (1994) Thymic CD45 tyrosine phosphatase regulates apoptosis and MHC-restricted negative selection. J Immunol 152:3793-3805
99. Karnitz L, Sutor SL, Torigoe T, Reed JC, Bell MP, McKean DJ, Leibson PJ, Abraham RT (1992) Effects of p56lck deficiency on the growth and cytolytic effector function of an interleukin-2-dependent cytotoxic T-cell line. Mol Cell Biol 12:4521-4530
100. Straus DB, Weiss A (1992) Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell 70:585-593
101. Cano E, Mahadevan LC (1995) Parallel signal processing among mammalian MAPKs. Trends Biochem Sci 20:117-122
102. Davis RJ (1994) MAPKs: new JNK expands the group. Trends Biochem Sci 19:470-473
103. Gulbins E, Bissonnette R, Mahboubi A, Martin S, Nishioka W, Brunner T, Baier G, Baier-Bitterlich G, Byrd C, Lang F, Kolesnick R, Altman A, Green D (1995) FAS-induced apoptosisis mediated via a ceramide-initiated RAS signaling pathway. Immunity 2:341-351
104. Downward J, Graves JD, Warne PH, Rayter S, Cantrell DA (1990) Stimulation of p21ras upon T-cell activation. Nature 346:719-723
105. Nel AE, Hanekom C, Hultin L (1991) Protein kinase C plays a role in the induction of tyrosine phosphorylation of lymphoid microtubule-associated protein-2 kinase. Evidence for a CD3-associated cascade that includes pp56lck and that is defective in HPB-ALL. J Immunol 147:1933-1939
106. Whitehurst CE, Boulton TG, Cobb MH, Geppert TD (1992) Extracellular signal-regulated kinases in T cells. Anti-CD3 and 4 beta-phorbol 12-myristate 13-acetate-induced phosphorylation and activation. J Immunol 148:3230-3237
107. Siegel JN, Klausner RD, Rapp UR, Samelson LE (1990) T cell antigen receptor engagement stimulates c-raf phosphorylation and induces c-raf-associated kinase activity via a protein kinase C-dependent pathway. J Biol Chem 265:18472-18480
108. Swan KA, Alberola-Ila J, Gross JA, Appleby MW, Forbush KA, Thomas JF, Perlmutter RM (1995) Involvement of p21ras distinguishes positive and negative selection in thymocytes. EMBO J 14:276-285
109. Alberola-Ila J, Forbush KA, Seger R, Krebs EG, Perlmutter RM (1995) Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373:620-623
110. Izquierdo Pastor M, Reif K, Cantrell D (1995) The regulation and function of p21ras during T-cell activation and growth. Immunol Today 16:159-164
111. Kizaki H, Tadakuma T, Odaka C, Muramatsu J, Ishimura Y (1989) Activation of a suicide process of thymocytes through DNA fragmentation by calcium ionophores and phorbol esters. J Immunol 143:1790-1794
112. Strasser A, Harris AW, Cory S (1991) bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67:889-899
113. McConkey DJ, Hartzell P, Nicotera P, Orrenius S (1989) Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J 3:1843-1849
114. Vasquez NJ, Kane LP, Hedrick SM (1994) Intracellular signals that mediate thymic negative selection. Immunity 1:45-56
115. Davis PD, Elliott LH, Harris W, Hill CH, Hurst SA, Keech E, Kumar MK, Lawton G, Nixon JS, Wilkinson SE (1992) Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity. J Med Chem 35:994-1001
116. Anderson G, Anderson KL, Conroy LA, Hallam TJ, Moore NC, Owen JJ, Jenkinson EJ (1995) Intracellular signaling events during positive and negative selection of CD4+CD8+ thymocytes in vitro. J Immunol 154:3636-3643
117. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F, et al (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem 266:15771-15781
118. Wilkinson SE, Parker PJ, Nixon JS (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J 294:(Pt 2):335-337
119. Martiny-Baron G, Kazanietz MG, Mischak H, Blumberg PM, Kochs G, Hug H, Marme D, Schachtele C (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J Biol Chem 268:9194-9197
120. Freire-Moar J, Cherwinski H, Hwang F, Ransom J, Webb D (1991) Expression of protein kinase C isoenzymes in thymocyte subpopulations and their differential regulation. J Immunol 147:405-409
121. Havran WL, Poenie M, Kimura J, Tsien R, Weiss A, Allison JP (1987) Expression and function of the CD3-antigen receptor on murine CD4+CD8+ thymocytes. Nature 330:170-173
122. 2+ in response to antigen receptor crosslinking. Nature 330:179-181
123. Nakayama T, Ueda Y, Yamada H, Shores EW, Singer A, June CH (1992) In vivo calcium elevations in thymocytes with T cell receptors that are specific for self ligands. Nature 357:695-697
124. Clipstone NA, Crabtree GR (1992) Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 356:695-697
125. O'Keefe SJ, Tamura J, Kincaid RL, Tocci MJ, O'Neill EA (1992) FK-506-and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 356:695-697
126. Gao EK, Lo D, Cheney R, Kanagawa O, Sprent J (1988) Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature 336:176-179
127. Hollander GA, Fruman DA, Bierer BE, Burakoff SJ (1994) Disruption of T cell development and repertoire selection by calcineurin inhibition in vivo. Transplantation 58:1037-1043
128. Shi YF, Sahai BM, Green DR (1989) Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature 339:625-626
129. Urdahl KB, Pardoll DM, Jenkins MK (1994) Cyclosporin A inhibits positive selection and delays negative selection in alpha beta TCR transgenic mice. J Immunol 152:2853-2859
130. Siegel RM, Katsumata M, Miyashita T, Louie DC, Greene MI, Reed JC (1992) Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice. Proc Natl Acad Sci USA 89:7003-7007
131. Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ (1991) bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67:879-888
132. Tao W, Teh SJ, Melhado I, Jirik F, Korsmeyer SJ, Teh HS (1994) The TG cell receptor repertoire of CD4-8+ thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus. J Exp Med 179:145-153
133. Strasser A, Harris AW, von Boehmer H, Cory S (1994) Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene. Proc Natl Acad Sci USA 91:1376-1380
134. Jameson SC, Hogquist KA, Bevan MJ (1995) Positive selection of thymocytes. Annu Rev Immunol 13:93-126
135. Allen JD, Harris AW, Bath ML, Strasser A, Scollay R, Adams JM (1995) Perturbed development of T and B cells in mice expressing an Hlx homeobox transgene. J Immunol 154:1531-1542
136. Lee NA, Loh DY, Lacy E (1992) CD8 surface levels alter the fate of alpha/ beta T cell receptor-expressing thymocytes in transgenic mice. J Exp Med 175:1013-1025
137. Robey EA, Ramsdell F, Kioussis D, Sha W, Loh D, Axel R, Fowlkes BJ (1992) The level of CD8 expression can determine the outcome of thymic selection. Cell 69:1089-1096
138. Malenka RC (1994) Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78:535-538
139. Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179-185
140. Defranco AL, Raveche ES, Asofsky R, Paul WE (1982) Frequency of B lymphocytes responsive to anti-immunoglobulin. J Exp Med 155:1523-1536