Signaling checkpoints during the development of T lymphocytes

Current Opinion in Immunology

Volumn 10, Issue 3, 1998, Pages 360-367

  Killeen, Nigel ^a   Irving, Bryan A ^a   Pippig, Susanne ^a   Zingler, Kurt ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; T LYMPHOCYTE RECEPTOR;

REVIEW; T LYMPHOCYTE; THYMOCYTE; THYMUS;

EID: 0031859665     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(98)80176-3     Document Type: Article

References (93)

1. Anderson G, Moore NC, Owen JJ, Jenkinson EJ. Cellular interactions in thymocyte development. Annu Rev Immunol. 14:1996;73-99.
2. Jameson SC, Hogquist KA, Bevan MJ. Positive selection of thymocytes. Annu Rev Immunol. 13:1995;93-126.
3. Ardavin C, Wu L, Li CL, Shortman K. Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature. 362:1993;761-763.
4. Rodewald HR, Moingeon P, Lucich JL, Dosiou C, Lopez P, Reinherz EL. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 69:1992;139-150.
5. Wu L, Antica M, Johnson GR, Scollay R, Shortman K. Developmental potential of the earliest precursor cells from the adult mouse thymus. J Exp Med. 174:1991;1617-1627.
6. Shortman K, Wu L. Early T lymphocyte progenitors. Annu Rev Immunol. 14:1996;29-47.
7. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, et al. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity. 2:1995;223-238.
8. DiSanto JP, Muller W, Guy-Grand D, Fischer A, Rajewsky K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci USA. 92:1995;377-381.
9. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med. 180:1994;1955-1960.
10. Rodewald HR, Kretzschmar K, Swat W, Takeda S. Intrathymically expressed c-Kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo. Immunity. 3:1995;313-319.
11. Von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med. 181:1995;1519-1526.
12. Rodewald HR, Ogawa M, Haller C, Waskow C, DiSanto JP. Pro-thymocyte expansion by c-Kit and the common cytokine receptor gamma chain is essential for repertoire formation. Immunity. 6:1997;265-272.
13. Von Freeden-Jeffry U, Solvason N, Howard M, Murray R. The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. of outstanding interest Immunity. 7:1997;147-154 This is a careful analysis showing that IL-7 upregulates Bcl-2 in triple-negative thymocytes and protects them from apoptosis.
14. Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. of outstanding interest Cell. 89:1997;1033-1041 This demonstrates that transgenic expression of Bcl-2 rescues thymocyte development in mice that lack the IL-7 receptor and that Bcl-2 expression is upregulated in thymocytes and lymphocytes treated with IL-7. It uses a novel in vivo assay to show that IL-7 is required for positive selection. See also von Freeden-Jeffry et al., 1997 [13], Kondo et al., 1997 [15] and Maraskovsky et al., 1997 [16].
15. Kondo M, Akashi K, Domen J, Sugamura K, Weissman Il. Bcl-2 rescues T lymphopoiesis, but not B or NK cell development in common gamma chain-deficient mice. of outstanding interest Immunity. 7:1997;155-162 This reports that transgenic expression of Bcl-2 rescues thymocyte development in mice that lack the common gamma chain, which is a signaling component of the receptor for IL-7 and other cytokines. See also von Freeden-Jeffry et al., 1997 [13], Akashi et al., 1997 [14] and Maraskovsky et al., 1997 [16].
16. Maraskovsky E, O'Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. of outstanding interest Cell. 89:1997;1011-1019 The authors show that transgenic expression of Bcl-2 rescues thymocyte development and T cell proliferative responses in mice that lack the IL-7 receptor. See also von Fredeen-Jeffry et al., 1997 [13], Akashi et al., 1997 [14] and Kondo et al., 1997 [15].
17. Galandrini R, Henning SW, Cantrell DA. Different functions of the GTPase Rho in prothymocytes and late pre-T cells. of outstanding interest Immunity. 7:1997;163-174 A detailed study that examines the impact of Rho inhibition on the development, survival and cell cycle of thymocytes at early stages in their development.
18. Henning SW, Galandrini R, Hall A, Cantrell DA. The GTPase Rho has a critical regulatory role in thymus development. EMBO J. 16:1997;2397-2407.
19. Oosterwegel MA, Haks MC, Jeffry U, Murray R, Kruisbeek AM. Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells. Immunity. 6:1997;351-360.
20. Washburn T, Schweighoffer E, Gridley T, Chang D, Fowlkes BJ, Cado D, Robey E. Notch activity influences the alphabeta versus gammadelta T cell lineage decision. of outstanding interest Cell. 88:1997;833-843 This reports that Notch signaling is implicated in the commitment of cells to the αβ versus γδ lineages.
21. Hasserjian RP, Aster JC, Davi F, Weinberg DS, Sklar J. Modulated expression of Notch1 during thymocyte development. Blood. 88:1996;970-976.
22. Robey E, Chang D, Itano A, Cado D, Alexander H, Lans D, Weinmaster G, Salmon P. An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. of outstanding interest Cell. 87:1996;483-492 This paper shows that commitment to the CD4 and CD8 lineages in influenced by signal transduction through Notch.
23. Von Boehmer H, Fehling HJ. Structure and function of the pre-T cell receptor. Annu Rev Immunol. 15:1997;433-452.
24. Fehling HJ, Krotkova A, Saint-Ruf C, von Boehmer H. Crucial role of the pre-T-cell receptor alpha gene in development of alpha beta but not gamma delta T cells. Nature. 375:1995;795-798. (Published erratum appears in Nature 1995, 378:419.].
25. Malissen M, Gillet A, Ardouin L, Bouvier G, Trucy J, Ferrier P, Vivier E, Malissen B. Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene. EMBO J. 14:1995;4641-4653.
26. Mombaerts P, Clarke AR, Rudnicki MA, Iacomini J, Itohara S, Lafaille JJ, Wang L, Ichikawa Y, Jaenisch R, Hooper ML, et al. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. [Published erratum appears in Nature 1992, 360:491.] Nature. 360:1992;225-231.
27. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 68:1992;869-877.
28. Shinkai Y, Koyasu S, Nakayama K, KM Murphy, Loh DY, Reinherz EL, Alt FW. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science. 259:1993;822-825.
29. Xu Y, Davidson L, Alt FW, Baltimore D. Function of the pre-T-cell receptor alpha chain in T-cell development and allelic exclusion at the T-cell receptor beta locus. Proc Natl Acad Sci USA. 93:1996;2169-2173.
30. of outstanding interest Aifantis I, Buer J, von Boehmer H, Azogui O. Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus. of special interest Immunity. 7:1997;601-607 This report is a careful single-cell analysis indicating that the pre-T α chain is required for allelic exclusion at the TCR β locus. This result and those presented in Krotkova et al., 1997 [31] and Ardouin et al., 1998 [32] underscore the key significance of pre-TCR signaling in the process of allelic exclusion.
31. of special interest Krotkova A, von Boehmer H, Fehling HJ. Allelic exclusion in pTalpha-deficient mice: no evidence for cell surface expression of two T cell receptor (TCR)-beta chains, but less efficient inhibition of endogeneous Vbeta→(D)Jbeta rearrangements in the presence of a functional TCR-beta transgene. of outstanding interest J Exp Med. 186:1997;767-775 This result and those presented in Arifantis et al., 1997 [30] and Ardouin et al., 1998 [32] underscore the key significance of pre-TCR signaling in the process of allelic exclusion.
32. of outstanding interest Ardouin L, Ismaili J, Malissen B, Malissen M. The CD3-γδε and CD3-ζ/η modules are each essential for allelic exclusion at the T cell receptor β locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-β, -γ, and -δ Loci. of special interest J Exp Med. 187:1998;105-116 This result and those presented in Arifantis et al., 1997 [30] and Krotkova et al., 1998 [31] underscore the key significance of pre-TCR signaling in the process of allelic exclusion.
33. Groves T, Smiley P, Cooke MP, Forbush K, Perlmutter RM, Guidos CJ. Fyn can partially substitute for Lck in T lymphocyte development. Immunity. 5:1996;417-428.
34. Levin SD, Anderson SJ, Forbush KA, Perlmutter RM. A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J. 12:1993;1671-1680.
35. lck. Nature. 357:1992;161-164.
36. Van Oers NS, Lowin-Kropf B, Finlay D, Connolly K, Weiss A. Alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases. Immunity. 5:1996;429-436.
37. Mombaerts P, Anderson SJ, Perlmutter RM, Mak TW, Tonegawa S. An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. Immunity. 1:1994;261-267.
38. Fehling HJ, Iritani BM, Krotkova A, Forbush KA, Laplace C, Perlmutter RM, von Boehmer H. Restoration of thymopoiesis in pT alpha-/- mice by anti-CD3epsilon antibody treatment or with transgenes encoding activated Lck or tailless pT alpha. Immunity. 6:1997;703-714.
39. Cheng AM, Negishi I, Anderson SJ, Chan AC, Bolen J, Loh DY, Pawson T. The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. of outstanding interest Proc Natl Acad Sci USA. 94:1997;9797-9801 This demonstrates that double-positive thymocytes do not develop in mice that lack both Syk and ZAP-70. This result indicates functional redundancy of these two protein tyrosine kinases in pre-TCR signaling.
40. + thymocytes, and B cell maturation. J Exp Med. 183:1996;1707-1718.
41. Vav. It demonstrates the effects of the null phenotype on thymocyte development at early and late stages consistent with Vav being a key component in TCR-dependent signal transduction.
42. O'Shea CC, Thornell AP, Rosewell IR, Hayes B, Owen MJ. Exit of the pre-TCR form the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thyocytes. Immunity. 7:1997;591-600.
43. Irving BI, Alt FW, Killeen N. Thymocyte development in the absence of pre-T cell receptor extracellular Ig domains. Science. 280:1998;905-909.
44. Okamura RM, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R. Redundant regulation of T cell differentiation and TCRα gene expression by the transcription factors LEF-1 and TCF-1. Immunity. 8:1998;11-20.
45. + distinguished in the early growth response (Egr)-1 transgenic mice with a recombinase-activating gene-deficient background. J Exp Med. 186:1997;877-885.
46. Bevan MJ. In thymic selection, peptide diversity gives and takes away. Immunity. 7:1997;175-178.
47. Alam SM, Travers PJ, Wung JL, Nasholds W, Redpath S, Jameson SC, Gascoigne NR. T-cell-receptor affinity and thymocyte positive selection. Nature. 381:1996;616-620.
48. Margulies DH. Interactions of TCRs with MHC-peptide complexes: a quantitative basis for mechanistic models. Curr Opin Immunol. 9:1997;390-395.
49. Shores EW, Love PE. TCR zeta chain in T cell development and selection. Curr Opin Immunol. 9:1997;380-389.
50. Killeen N, Littman DR. Helper T-cell development in the absence of CD4-p56lck association. Nature. 364:1993;729-732.
51. Teh HS, Garvin AM, Forbush KA, Carlow DA, Davis CB, Littman DR, Perlmutter RM. Participation of CD4 coreceptor molecules in T-cell repertoire selection. Nature. 349:1991;241-243.
52. Negishi I, Motoyama N, Nakayama K, Nakayama K, Senju S, Hatakeyama S, Zhang O, Chan AC, Loh DY. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature. 376:1995;435-438.
53. Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR. Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature. 385:1997;169-172.
54. Teramoto H, Salem P, Robbins KC, Bustelo XR, Gutkind JS. Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway. J Biol Chem. 272:1997;10751-10755.
55. + thymocytes. Nature. 374:1995;474-477.
56. Tarakhovsky A, Turner M, Schaal S, Mee PJ, Duddy LP, Rajewsky K, Tybulewicz VL. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature. 374:1995;467-470.
57. Zhang R, Alt FW, Davidson L, Orkin SH, Swat W. Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav photo-oncogene. Nature. 374:1995;470-473.
58. Lucas B, Vasseur F, Penit C. Production, selection, and maturation of thymocytes with high surface density of TCR. J Immunol. 153:1994;53-62.
59. Davis CB, Littman DR. Thymocyte lineage commitment: is it instructed or stochastic? Curr Opin Immunol. 6:1994;266-272.
60. Robey E, Fowlkes BJ. Selective events in T cell development. Annu Rev Immunol. 12:1994;675-705.
61. Ksnig R, Huang L-Y, Germain RN. MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8. Nature. 356:1992;796-798.
62. Salter RD, Norment AM, Chen BP, Clayberger C, Krensky AM, Littman DR, Parham P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 338:1989;345-347.
63. Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci USA. 85:1988;5190-5194.
64. Turner JM, Brodsky MH, Irving BA, Levin SD, Perlmutter RM, Littman DR. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 60:1990;755-765.
65. Veillette A, Bookman MA, Horak EM, Bolen JB. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 55:1988;301-308.
66. Fung-Leung WP, Schilham MW, Rahemtulla A, Kundig TM, Vollenweider M, Potter J, van Ewijk W, Mak TW. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 65:1991;443-449.
67. Chan IT, Limmer A, Louie MC, Bullock ED, Fung-Leung WP, Mak TW, Loh DY. Thymic selection of cytotoxic T cells independent of CD8 alpha-Lck association. Science. 261:1993;1581-1584.
68. Goldrath AW, Hogquist KA, Bevan MJ. CD8 lineage commitment in the absence of CD8. of outstanding interest Immunity. 6:1997;633-642 This paper and that by Sebzda et al., 1997 [69] shows that the CD8 molecule is not absolutely essential for commitment to the CD8 lineage.
69. Sebzda E, Choi M, Fung-Leung WP, Mak TW, Ohashi PS. Peptide-induced positive selection of TCR transgenic thymocytes in a coreceptor-independent manner. of outstanding interest Immunity. 6:1997;643-653 This paper and that by Goldrath et al., 1997 [68] shows that the CD8 molecule is not absolutely essential for commitment to the CD8 lineage.
70. Locksley RM, Reiner SL, Hatam F, Littman DR, Killeen N. Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science. 261:1993;1448-1451.
71. Rahemtulla A, Kundig TM, Narendran A, Bachmann MF, Julius M, Paige CJ, Ohashi PS, Zinkernagel RM, Mak TW. Class II major histocompatibility complex-restricted T cell function in CD4-deficient mice. Eur J Immunol. 24:1994;2213-2218.
72. Itano A, Salmon P, Kioussis D, Tolaini M, Corbella P, Robey E. The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells. J Exp Med. 183:1996;731-741.
73. Matechak EO, Killeen N, Hedrick SM, Fowlkes BJ. MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent. Immunity. 4:1996;337-347.
74. + mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8α chain in mice but not rats. of special interest J Immunology. 160:1998;700-707 This report shows a potentially revealing difference between rat and mouse double-positive thymocytes in their choice of lineage when differentiated with phorbol ester and ionomycin or anti-TCR antibodies.
75. + thymocytes in suspension culture. Eur J Immunol. 26:1996;2081-2086.
76. Takahama Y, Nakauchi H. Phorbol ester and calcium ionophore can replace TCR signals that induce positive selection of CD4 T cells. J Immunol. 157:1996;1508-1513.
77. Alberola-Ila J, Forbush KA, Seger R, Krebs EG, Perlmutter RM. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature. 373:1995;620-623.
78. Alberola-Ila J, Hogquist KA, Swan KA, Bevan MJ, Perlmutter RM. Positive and negative selection invoke distinct signaling pathways. J Exp Med. 184:1996;9-18.
79. Crompton T, Gilmour KC, Owen MJ. The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell. 86:1996;243-521.
80. Sharp LL, Schwarz DA, Bott CM, Marshall CJ, Hedrick SM. The influence of the MAPK pathway on T cell lineage commitment. of outstanding interest Immunity. 7:1997;609-618 This provides evidence that the relative involvement of mitogen-activated protein kinase (MAPK) signaling may influence CD4/CD8 lineage commitment.
81. Benoist C, Mathis D. T-cell co-receptors. The end of a frustrating search. Curr Biol. 4:1994;821-823.
82. Ellmeier W, Sunshine MJ, Losos K, Hatam F, Littman DR. An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells. of outstanding interest Immunity. 7:1997;537-547 This paper and that of Hostert et al., 1997 [83] describe the identification of a cis-acting sequence in the CD8 locus that activates transcription of reporter transgenes in positively-selected CD8 lineage thymocytes and T cells.
83. Hostert A, Tolaini M, Roderick K, Harker N, Norton T, Kioussis D. A region in the CD8 gene locus that directs expression to the mature CD8 T cell subset in transgenic mice. of outstanding interest Immunity. 7:1997;525-536 This paper and that of Ellmeier et al., 1997 [82] describe the identification of a cis-acting sequence in the CD8 locus that activates transcription of reporter transgenes in positively-selected CD8 lineage thymocytes and T cells.
84. Cibotti R, Punt JA, Dash KS, Sharrow SO, Singer A. Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage-specific signals. Immunity. 6:1997;245-255.
85. Muller KP, Kyewski BA. Intrathymic T cell receptor (TcR) targeting in mice lacking CD4 or major histocompatibility complex (MHC) class II: rescue of CD4 T cell lineage without co-engagement of TcR/CD4 by MHC class II. Eur J Immunol. 25:1995;896-902.
86. Muller KP, Kyewski BA. T cell receptor targeting to thymic cortical epithelial cells in vivo induces survival, activation and differentiation of immature thymocytes. Eur J Immunol. 23:1993;1661-1670.
87. Schmitt S, Muller KP, Kyewski BA. Two separable T cell receptor signals reconstitute positive selection of CD4 lineage T cells in vivo. Eur J Immunol. 27:1997;2136-2144.
88. of outstanding interest Nakano N, Rooke R, Benoist C, Mathis D. Positive selection of T cells induced by viral delivery of neopeptides to the thymus. of special interest Science. 275:1997;678-683 This provides a novel approach for inducing the positive selection of thymocytes in vivo which also includes a determination of the amount of time between positive selection and emigration to the periphery. See also the earlier discussion of this issue in Scollay and Godfrey, 1995 [89] and in Tough and Sprent, 1997 [90] and the related work in Penit and Vasseur, 1997 [91].
89. Scollay R, Godfrey DI. Thymic emigration: conveyor belts or lucky dips? Immunol Today. 16:1995;268-273.
90. Tough D, Sprent J. Thymic emigration-reply. Immunol Today. 16:1995;273-274.
91. Penit C, Vasseur F. Expansion of mature thymocyte subsets before emigration to the periphery. of special interest J Immunol. 159:1997;4848-4856 This is a careful kinetic analysis arguing that a significant fraction of mature thymocytes undergo proliferation before exit to the periphery.
92. Yagi H, Matsumoto M, Nakamura M, Makino S, Suzuki R, Harada M, Itoh T. Defect of thymocyte emigration in a T cell deficiency strain (CTS) of the mouse. J Immunol. 157:1996;3412-3419.
93. Corcoran AE, Riddell A, Krooshoop D, Venkitaraman AR. Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature. 391:1998;904-907.