Cell-fate decisions in early T cell development: Regulation by cytokine receptors and the pre-TCR

Seminars in Immunology

Volumn 11, Issue 1, 1999, Pages 23-37

  Haks, Mariëlle C ^b   Oosterwegel, Mariëtte A ^b   Blom, Bianca ^b   Spits, Hergen ^b   Kruisbeek, Ada M ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b NONE

Author keywords

Early T cell development; IL 7 receptor; Pre T cell receptor

Indexed keywords

CYTOKINE RECEPTOR; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; T LYMPHOCYTE RECEPTOR;

ARTICLE; B LYMPHOCYTE; BONE MARROW; BONE MARROW CELL; CELL SURVIVAL; GENE EXPRESSION; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; LYMPHOID CELL; NONHUMAN; SIGNAL TRANSDUCTION; STROMA CELL; T LYMPHOCYTE; THYMOCYTE; THYMUS;

EID: 0005752771     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1006/smim.1998.0153     Document Type: Article

References (143)

1. Wu L, Scollay R, Egerton M, Pearse M, Spangrude GJ, Shortman K (1991) CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature 349:71-74
2. Ardavin C, Wu L, Li C-L, Shortman K (1993) Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature 362:761-763
3. - triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol 150:4244-4252
4. Carlyle JR, Michie AM, Furlonger C, Nakano T, Lenardo MJ, Paige CJ, Zúniga-Pflücker JC (1997) Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes. J Exp Med 186:173-182
5. - thymocyte differentiation. J Immunol 152:4783-4792
6. Wilson A, Held W, MacDonald HR (1994) Two waves of recombinase gene expression in developing thymocytes. J Exp Med 179:1355-1360
7. Shortman K, Wu L (1996) Early T lymphocyte progenitors. Annu Rev Immunol 14:29-47
8. Malissen B, Malissen M (1996) Functions of TCR and pre-TCR subunits: Lessons from gene ablation. Curr Opin Immunol 8:383-393
9. Fehling HJ, Von Boehmer H (1997) Early αβ T cell development in the thymus of normal and genetically altered mice. Curr Opin Immunol 9:263-275
10. Hoffman ES, Passoni L, Crompton T, Leu TMJ, Schatz DG, Koff A, Owen MJ, Hayday AC (1996) Productive T-cell receptor β-chain gene rearrangement: Coincident regulation of cell cycle and clonality during development in vivo. Genes Dev 10:948-962
11. Borst J, Jacobs H, Brouns G (1996) Composition and function of T-cell receptor and B-cell receptor complexes on precursor lymphocytes. Curr Opin Immunol 8:181-190
12. Kisielow P, Von Boehmer H (1995) Development and selection of T cells: Facts and puzzles. Adv Immunol 58:87-209
13. + T cells. Curr Opin Immunol 8:225-232
14. Amsen D, Kruisbeek AM (1998) Thymocyte selection: Not by TCR alone. Immunol Rev, in Press
15. Di Santo JP, Rodewald H-R (1998) In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development. Curr Opin Immunol 10:196-207
16. +) thymocytes in normal and genetically modified mice. J Immunol 154:5103-5113
17. Falk I, Biro J, Kohler H, Eichmann K (1996) Proliferation kinetics associated with T cell receptor-β chain selection of fetal murine thymocytes. J Exp Med 184:2327-2339
18. Zlotnik A, Moore TA (1995) Cytokine production and requirements during T-cell development. Curr Opin Immunol 7:206-213
19. Von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SEG, Murray R (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies Il-7 as a nonredundant cytokine. J Exp Med 181:1519-1526
20. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180:1955-1960
21. Maki K, Sunaga S, Komagata Y, Kodaira Y, Mabuchi A, Karasuyama H, Yokomuro K, Miyazaki J-I, Ikuta K (1996) Interleukin 7 receptor-deficient mice lack γδ T cells. Proc Natl Acad Sci USA 93:7172-7177
22. O'Shea JJ (1997) Jaks, STATs, cytokine signal transduction, and immunoregulation: Are we there yet? Immunity 7:1-11
23. Ivashkiv LB (1995) Cytokines and STATs: How can signals achieve specificity? Immunity 3:1-4
24. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O (1995) Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 13:369-398
25. Eynon EE, Kuida K, Flavell RA (1996) Disruption of cytokine signaling in lymphoid development: Unique contributions of the common cytokine gamma chain and the Jak3 kinase. J Interferon Cytokine Res 16:677-684
26. DiSanto JP, Müller W, Guy-Grand D, Fischer A, Rajewsky K (1995) Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor γ chain. Proc Natl Acad Sci USA 92:377-381
27. Ohbo K, Suda T, Hashiyama M, Mantani A, Ikebe M, Miyakawa K, Moriyama M, Nakamura M, Katsuki M, Takahashi K, Yamamura K-I, Sugamura K (1996) Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. Blood 87:956-967
28. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, Paul WE, Katz SI, Love PE, Leonard WJ (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. Immunity 2:223-238
29. Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771-782
30. Thomis DC, Gurniak CB, Tivol E, Sharpe AH, Berg LJ (1995) Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science 270:794-797
31. Nosaka T, Van Deursen JMA, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP, Doherty PC, Grosveld GC, Ihle JN (1995) Defective lymphoid development in mice lacking Jak3. Science 270:800-802
32. Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KCF, Yin L, Pennica D, Johnson Jr. EM, Schreiber RD (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 93:373-383
33. -/- mice. J Immunol 157:2366-2373
34. He Y-W, Nakajima H, Leonard WJ, Adkins B, Malek TR (1997) The common γ-chain of cytokine receptors regulates intrathymic T cell development at multiple stages. J Immunol 158:2592-2599
35. Eynon EE, Livák F, Kuida K, Schatz DG, Flavell RA (1998) Distinct effects of JAK3 signaling on αβ and γδ thymocyte development. J Immunol, in Press
36. Ray RJ, Furlonger C, Williams DE, Paige CJ (1996) Characterization of thymic stromal-derived lymphopoietin (TSLP) in murine B cell development in vitro. Eur J Immunol 26:10-16
37. + B cells and produces a novel growth factor affecting B and T lineage cells. Exp Hematol 22:321-328
38. Lantz O, Sharara LI, Tilloy F, Andersson Å, DiSanto JP (1997) Lineage relationships and differentiation of natural killer (NK) T cells: Intrathymic selection and interleukin (IL)-4 production in the absence of NKR-P1 and Ly49 molecules. J Exp Med 185:1395-1401
39. Godfrey DI, Zlotnik A, Suda T (1992) Phenotypic and functional characterization of c-kit expression during intrathymic T cell development. J Immunol 149:2281-2285
40. Galli SJ, Zsebo KM, Geissler EN (1994) The kit ligand, stem cell factor. Adv Immunol 55:1-96
41. Rodewald H-R, Kretzschmar K, Swat W, Takeda S (1995) Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo. Immunity 3:313-319
42. Asamoto H, Mandel TE (1981) Thymus in mice bearing the steel mutation. Morphologic studies on fetal, neonatal, organ-cultured, and grafted fetal thymus. Lab Invest 45:418-426
43. Rodewald H-R, Ogawa M, Haller C, Waskow C, DiSanto JP (1997) Pro-thymocyte expansion by c-kit and the common cytokine receptor γ chain is essential for repertoire formation. Immunity 6:265-272
44. Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S, Cosman D, Goodwin RG (1988) Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333:571-573
45. Conlon PJ, Morrissey PJ, Nordan RP, Grabstein KH, Prickelt KS, Reed SG, Goodwin R, Cosman D, Namen AE (1989) Murine thymocytes proliferate in direct response to interleukin-7. Blood 74:1368-1373
46. Murray R, Suda T, Wrighton N, Lee F, Zlotnik A (1989) IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int Immunol 1:526-531
47. Watson JD, Morrissey PJ, Namen AE, Conlon PJ, Widmer MB (1989) Effect of IL-7 on the growth of fetal thymocytes in culture. J Immunol 143:1215-1222
48. Von Freeden-Jeffry U, Solvason N, Howard M, Murray R (1997) The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7:147-154
49. Kim K, Lee C-K, Sayers TJ, Muegge K, Durum SK (1998) The trophic action of IL-7 on pro-T cells: Inhibition of apoptosis of pro-T1, -T2, and -T3 cells correlates with Bcl-2 and Bax levels and is independent of Fas and p53 pathways. J Immunol 160:5735-5741
50. + stage during positive selection and promotes thymocyte differentiation at several control points. Immunity 1:197-205
51. Moore NC, Anderson G, Williams GT, Owen JJT, Jenkinson EJ (1994) Developmental regulation of bcl-2 expression in the thymus. Immunology 81:115-119
52. Gratiot-Deans J, Merino R, Nuñez G, Turka LA (1994) Bcl-2 expression during T-cell development: Early loss and late return occur at specific stages of commitment to differentiation and survival. Proc Natl Acad Sci USA 91:10685-10689
53. Akashi K, Kondo M, Von Freeden-Jeffry U, Murray R, Weissman IL (1997) Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89:1033-1041
54. -/- mice. Cell 89:1011-1019
55. Kondo M, Akashi K, Domen J, Sugamura K, Weissman IL (1997) Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common γ chain-deficient mice. Immunity 7:155-162
56. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229-240
57. Henning SW, Cantrell DA (1998) GTPases in antigen receptor signalling. Curr Opin Immunol 10:322-329
58. Galandrini R, Henning SW, Cantrell DA (1997) Different functions of the GTPase Rho in prothymocytes and late pre-T cells. Immunity 7:163-174
59. Henning SW, Galandrini R, Hall A, Cantrell DA (1997) The GTPase Rho has a critical regulatory role in thymus development. EMBO J 16:2397-2407
60. Candéias S, Muegge K, Durum SK (1997) IL-7 receptor and VDJ recombination: Trophic versus mechanistic actions. Immunity 6:501-508
61. Tsuda S, Rieke S, Hashimoto Y, Nakauchi H, Takaham Y (1996) IL-7 supports D-J but not V-DJ rearrangement of TCR-β gene in fetal liver progenitor cells. J Immunol 156:3233-3242
62. Appasamy PM, Kenniston Jr. TW, Weng Y, Holt EC, Kost J, Chambers WH (1993) Interleukin 7-induced expression of specific T cell receptor γ variable region genes in murine fetal liver cultures. J Exp Med 178:2201-2206
63. Oosterwegel MA, Haks MC, Jeffry U, Murray R, Kruisbeek AM (1997) Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class II-expressing thymic stromal cells. Immunity 6:351-360
64. Maki K, Sunaga S, Ikuta K (1996) The V-J recombination of T cell receptor-γ genes is blocked in interleukin-7 receptor-deficient mice. J Exp Med 184:2423-2427
65. Candéias S, Peschon JJ, Muegge K, Durum SK (1997) Defective T-cell receptor γ gene rearrangement in interleukin-7 receptor knockout mice. Immunol Lett 57:9-14
66. Perumal NB, Kenniston Jr. TW, Tweardy DJ, Dyer KF, Hoffman R, Peschon J, Appasamy PM (1997) TCR-γ genes are rearranged but not transcribed in IL-7R α-deficient mice. J Immunol 158:5744-5750
67. Malissen M, Pereira P, Gerber DJ, Malissen B, DiSanto JP (1997) The common cytokine receptor γ chain controls survival of γ/δ T cells. J Exp Med 186:1277-1285
68. Crompton T, Outram SV, Buckland J, Owen MJ (1997) A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor α chain-deficient mice. Eur J Immunol 27:100-104
69. Mombaerts P, Clarke AR, Rudnicki MA, Iacomini J, Itohara S, Lafaille JJ, Wang L, Ichikawa Y, Jaenisch R, Hooper ML, Tonegawa S (1992) Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages. Nature 360:225-231
70. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE (1992) RAG-1 deficient mice have no mature B and T lymphocytes. Cell 68:869-877
71. Shinkai Y, Rathbun G, Lam K-P, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM, Alt FW (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855-867
72. Shinkai Y, Koyasu S, Nakayama K-I, Murphy KM, Loh DY, Reinherz EL, Alt FW (1993) Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science 259:822-825
73. Dudley EC, Petrie HT, Shah LM, Owen MJ, Hayday AC (1994) T cell receptor β chain gene rearrangement and selection during thymocyte development in adult mice. Immunity 1:83-93
74. Krotkova A, Von Boehmer H, Fehling HJ (1997) Allelic exclusion in pTα-deficient mice: No evidence for cell surface expression of two T cell receptor (TCR)-β chains, but less efficient inhibition of endogenous Vβ-> (D)Jβ rearrangements in the presence of a functional TCR-β transgene. J Exp Med 186:767-775
75. Aifantis I, Buer J, Von Boehmer H, Azogui O (1997) Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor β locus. Immunity 7:601-607
76. Ardouin L, Ismaili J, Malissen B, Malissen M (1998) 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. J Exp Med 187:105-116
77. Groettrup M, Ungewiss K, Azogui O, Palacios R, Owen MJ, Hayday AC, Von Boehmer H (1993) A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor β chain and a 33 kd glycoprotein. Cell 75:283-294
78. Saint-Ruf C, Ungewiss K, Groettrup M, Bruno L, Fehling HJ, Von Boehmer H (1994) Analysis and expression of a cloned pre-T cell receptor gene. Science 266:1208-1212
79. Van Oers NSC, Von Boehmer H, Weiss A (1995) The pre-T cell receptor (TCR) complex is functionally coupled to the TCR-ζ subunit. J Exp Med 182:1585-1590
80. Jacobs H, Vandeputte D, Tolkamp L, De Vries E, Borst J, Berns A (1994) CD3 components at the surface of pro-T cells can mediate pre-T cell development in vivo. Eur J Immunol 24:934-939
81. Berger MA, Davé V, Rhodes MR, Bosma GC, Bosma MJ, Kappes DJ, Wiest DL (1997) Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3δ is physically associated but not functionally required. J Exp Med 186:1461-1467
82. Fehling HJ, Krotkova A, Saint-Ruf C, Von Boehmer H (1995) Crucial role of the pre-T-cell receptor α gene in development of αβ but not γδ T cells. Nature 375:795-798
83. Dave VP, Cao Z, Browne C, Alarcon B, Fernandez-Miguel G, Lafaille J, De la Hera A, Tonegawa S, Kappes DJ (1997) CD3δ deficiency arrests development of the αβ but not the γδ T cell lineage. EMBO J 16:1360-1370
84. Malissen M, Gillet A, Ardouin L, Bouvier G, Trucy J, Ferrier P, Vivier E, Malissen B (1995) Altered T cell development in mice with a targeted mutation of the CD3-ε gene. EMBO J 14:4641-4653
85. Haks MC, Krimpenfort P, Borst J, Kruisbeek AM (1998) The CD3γ chain is essential for development of both the TCRαβ and TCRγδ lineages. EMBO J 17:1871-1882
86. Shores EW, Love PE (1997) TCR ζ chain in T cell development and selection. Curr Opin Immunol 9:380-389
87. Love PE, Shores EW, Johnson MD, Tremblay ML, Lee EJ, Grinberg A, Huang SP, Singer A, Westphal H (1993) T cell development in mice that lack the ζ chain of the T cell antigen receptor complex. Science 261:918-921
88. Malissen M, Gillet A, Rocha B, Trucy J, Vivier E, Boyer C, Köntgen F, Brun N, Mazza G, Spanopoulou E, Guy-Grand D, Malissen B (1993) T cell development in mice lacking the CD3-ζ/η gene. EMBO J 12:4347-4355
89. Ohno H, Aoe T, Taki S, Kitamura D, Ishida Y, Rajewsky K, Saito T (1993) Developmental and functional impairment of T cells in mice lacking CD3ζ chains. EMBO J 12:4357-4366
90. -/- mutant mice and identification of a novel T cell population in the intestine. EMBO J 12:4863-4875
91. Shores EW, Ono M, Kawabe T, Sommers CL, Tran T, Lui K, Udey MC, Ravetch J, Love PE (1998) T cell development in mice lacking all T cell receptor ζ family members (ζ, η, and FcεRIγ). J Exp Med 187:1093-1101
92. Shores EW, Huang K, Tran T, Lee E, Grinberg A, Love PE (1994) Role of TCR ζ chain in T cell development and selection. Science 266:1047-1050
93. O'Shea CC, Thornell AP, Rosewell IR, Hayes B, Owen MJ (1997) Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes. Immunity 7:591-599
94. Irving BA, Alt FW, Killeen N (1998) Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains. Science 280:905-908
95. Jacobs H, Ossendorp F, De Vries E, Ungewiss K, Von Boehmer H, Borst J, Berns A (1996) Oncogenic potential of a pre-T cell receptor lacking the TCRβ variable domain. Oncogene 12:2089-2099
96. Takase K, Wakizaka K, Von Boehmer H, Wada I, Moriya H, Saito T (1997) A novel 12 kilodalton dimer associated with pre-TCR complex and clonotype-independent CD3 complex on immature thymocytes. J Immunol 159:741-747
97. Levelt CN, Mombaerts P, Iglesias A, Tonegawa S, Eichmann K (1993) Restoration of early thymocyte differentiation in T-cell receptor β-chain-deficient mutant mice by transmembrane signaling through CD3ε. Proc Natl Acad Sci USA 90:11401-11405
98. -/- mice in the absence of TCR β chain expression. Int Immunol 6:995-1001
99. Levelt CN, Wang B, Ehrfeld A, Terhorst C, Eichmann K (1995) Regulation of T cell receptor (TCR)-β locus allelic exclusion and initiation of TCR-α locus rearrangement in immature thymocytes by signaling through the CD3 complex. Eur J Immunol 25:1257-1261
100. -/- mice by anti-CD3ε antibody treatment or with transgenes encoding activated Lck or tailless pTα. Immunity 6:703-714
101. Cambier JC (1995) Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM). J Immunol 155:3281-3285
102. Shores EW, Tran T, Grinberg A, Sommers CL, Shen H, Love PE (1997) Role of the multiple T cell receptor (TCR)-ζ chain signaling motifs in selection of the T cell repertoire. J Exp Med 185:893-900
103. Combadière B, Freedman M, Chen L, Shores EW, Love P, Lenardo MJ (1996) Qualitative and quantitative contributions of the T cell receptor ζ chain to mature T cell apoptosis. J Exp Med 183:2109-2117
104. Osman N, Turner H, Lucas S, Reif K, Cantrell DA (1996) The protein interactions of the immunoglobulin receptor family tyrosine-based activation motifs present in the T cell receptor ζ subunits and the CD3 γ,δ and ε chains. Eur J Immunol 26:1063-1068
105. Sunder-Plassmann R, Lialios F, Madsen M, Koyasu S, Reinherz EL (1997) Functional analysis of immunoreceptor tyrosine-based activation motif (ITAM)-mediated signal transduction: The two YxxL segments within a single CD3ζ-ITAM are functionally distinct. Eur J Immunol 27:2001-2009
106. Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, Neel BG, Birge RB, Fajardo JE, Chou MM, Hanafusa H, Schaffhausen B, Cantley LC (1993) SH2 domains recognize specific phosphopeptide sequences. Cell 72:767-778
107. Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, Barbacid M, Sabe H, Hanafusa H, Yi T, Ren R, Baltimore D, Ratnofsky S, Feldman RA, Cantley LC (1994) Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol 14:2777-2785
108. Letourneur F, Klausner RD (1992) A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains. Cell 69:1143-1157
109. Kishihara K, Penninger J, Wallace VA, Kündig 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
110. + thymocytes, and in B cell maturation. J Exp Med 183:1707-1718
111. Neel BG (1997) Role of phosphatases in lymphocyte activation. Curr Opin Immunol 9:405-420
112. Stone JD, Conroy LA, Byth KF, Hederer RA, Howlett S, Takemoto Y, Holmes N, Alexander DR (1997) Aberrant TCR-mediated signaling in CD45-null thymocytes involves dysfunctional regulation of Lck, Fyn, TCR-ζ, and ZAP-70. J Immunol 158:5773-5782
113. lck. Nature 357:161-164
114. lck controls allelic exclusion of T-cell receptor β-chain genes. Nature 365:552-554
115. lck deficient mice: Allelic exclusion of the TcR β locus is incomplete but thymocyte development is not restored by TcR β or TcR αβ transgenes. Eur J Immunol 25:1312-1318
116. Mombaerts P, Anderson SJ, Perlmutter RM, Mak TW, Tonegawa S (1994) An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. Immunity 1:261-267
117. Schmedt C, Saijo K, Niidome T, Kühn R, Aizawa S, Tarakhovsky A (1998) Csk controls antigen receptor-mediated development and selection of T-lineage cells. Nature 394:901-904
118. fyn. Cell 70:751-763
119. Groves T, Smiley P, Cooke MP, Forbush K, Perlmutter RM, Guidos CJ (1996) Fyn can partially substitute for Lck in T lymphocyte development. Immunity 5:417-428
120. Van Oers NSC, Lowin-Kropf B, Finlay D, Connolly K, Weiss A (1996) αβ T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases. Immunity 5:429-436
121. Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VlJ (1995) Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378:298-302
122. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T (1995) Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378:303-306
123. 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
124. Wiest DL, Ashe JM, Howcroft TK, Lee H-M, Kemper DM, Negishi I, Singer DS, Singer A, Abe R (1997) A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity 6:663-671
125. -/- mice by the Syk protein tyrosine kinase. Immunity 7:369-377
126. Cheng AM, Negishi I, Anderson SJ, Chan AC, Bolen J, Loh DY, Pawson T (1997) The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. Proc Natl Acad Sci USA 94:9797-9801
127. + thymocytes. Proc Natl Acad Sci USA 93:4683-4687
128. + thymocytes. Nature 374:474-477
129. Zhang R, Alt FW, Davidson L, Orkin SH, Swat W (1995) Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature 374:470-473
130. Tarakhovsky A, Turner M, Schaal S, Mee PJ, Duddy LP, Rajewsky K, Tybulewicz VlJ (1995) Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 374:467-470
131. Turner M, Mee PJ, Walters AE, Quinn ME, Mellor AL, Zamoyska R, Tybulewicz VlJ (1997) A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes. Immunity 7:451-460
132. Yablonski D, Kuhne MR, Kadlecek T, Weiss A (1998) Uncoupling of nonreceptor tyrosine kinases from PLC-γ1 in an SLP-76-deficient T cell. Science 281:413-416
133. Clements JL, Yang B, Ross-Barta SE, Eliason SL, Hrstka RF, Williamson RA, Koretzky GA (1998) Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science 281:416-419
134. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE (1998) LAT: The ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92:83-92
135. Crompton T, Gilmour KC, Owen MJ (1996) The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell 86:243-251
136. 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
137. Corcoran AE, Smart FM, Cowling RJ, Crompton T, Owen MJ, Venkitaraman AR (1996) The interleukin-7 receptor α chain transmits distinct signals for proliferation and differentiation during B lymphopoiesis. EMBO J 15:1924-1932
138. + stage of thymocyte differentiation in the absence of T cell receptor rearrangement. J Exp Med 183:1923-1928
139. + thymocytes in RAG-deficient mice through a T cell receptor β chain-independent pathway. J Exp Med 181:1187-1195
140. Bogue MA, Zhu C, Aguilar-Cordova E, Donehower LA, Roth DB (1996) p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Gene Dev 10:553-565
141. Jacks T (1996) Lessons from the p53 mutant mouse. J Cancer Res Clin Oncol 122:319-327
142. Lin W-C, Desiderio S (1993) Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. Science 260:953-959
143. Lin W-C, Desiderio S (1994) Cell cycle regulation of V(D)J recombination-activating protein RAG-2. Proc Natl Acad Sci USA 91:2733-2737