In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development

Current Opinion in Immunology

Volumn 10, Issue 2, 1998, Pages 196-207

  Di Santo, James P ^a   Rodewald, Hans Reimer ^b  

^a INSERM   (France)

^b BASEL INSTITUTE FOR IMMUNOLOGY   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; CYTOKINE RECEPTOR; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; PROTEIN TYROSINE KINASE; STEM CELL FACTOR; STEM CELL FACTOR RECEPTOR; T LYMPHOCYTE RECEPTOR;

CELL INTERACTION; CELL SURVIVAL; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; MUTANT; NATURAL KILLER CELL; REVIEW; SIGNAL TRANSDUCTION; STROMA CELL; T LYMPHOCYTE; THYMOCYTE;

EID: 0031956471     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(98)80249-5     Document Type: Article

References (99)

1. Malissen B, Malissen M. Functions of TCR and pre-TCR subunits: lessons from gene ablation. Curr Opin Immunol. 8:1996;383-393.
2. Rodewald H-R, Fehling HJ. Molecular and cellular events in early thymocyte development. Adv Immunol. 1998;. in press.
3. Shortman K, Wu L. Early T lymphocyte progenitors. Annu Rev Immunol. 14:1996;29-47.
4. of special interest Fehling HJ, Boehmer H. Early αβ T cell development in the thymus of normal and genetically altered mice. Curr Opin Immunol. 9:1997;263-275 A recent review focusing on early events in αβ T-cell development with an emphasis on the function of the pre-TCR.
5. Trowbridge IS, Lesley J, Trotter J, Hyman R. Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor β-chain gene. Nature. 315:1985;666-669.
6. Pearse M, Wu L, Egerton M, Wilson A, Shortman K, Scollay R. A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2-receptor. Proc Natl Acad Sci USA. 86:1989;1614-1618.
7. - murine thymocytes: in vivo development kinetics and T cell receptor β chain rearrangement status. J Exp Med. 177:1993;1079-1092.
8. Godfrey DI, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A. Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. J Immunol. 152:1994;4783-4792.
9. Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor β-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes Dev. 10:1996;948-962.
10. Petrie HT, Livak F, Burtrum D, Mazel S. T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. J Exp Med. 182:1995;121-127.
11. Tourigny MR, Mazel S, Burtrum DB, Petrie HT. T cell receptor (TCR)-β gene recombination: dissociation from cell cycle regulation and developmental progression during T cell ontogeny. J Exp Med. 185:1997;1549-1556.
12. 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. Immunity. 7:1997;601-607.
13. 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. J Exp Med. 186:1997;767-775.
14. Kisielow P, Von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol. 58:1995;87-209.
15. Zlotnik A, Moore TA. Cytokine production and requirements during T-cell development. Curr Opin Immunol. 7:1995;206-213.
16. Thomis DC, Berg LJ. The role of Jak3 in lymphoid development, activation and signaling. Curr Opin Immunol. 9:1997;541-547.
17. Cheng AM, Chan AC. Protein tyrosine kinases in thymocyte development. Curr Opin Immunol. 9:1997;528-533.
18. Galli SJ, Zsebo KM, Geissler EN. The kit ligand, stem cell factor. Adv Immunol. 55:1994;1-96.
19. Wu L, Scollay R, Egerton M, Pearse M, Spangrude GJ, Shortman K. CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature. 3:1991;71-74.
20. Moore TA, Zlotnik A. T cell lineage commitment and cytokine responses of thymic progenitors. Blood. 86:1995;1850-1860.
21. Kitamura Y, Tsujimura T, Jippo T, Kasugai T, Kanakura Y. Regulation of development, survival and neoplastic growth of mast cells through the c-kit receptor. Int Arch Allergy Immunol. 107:1995;54-56.
22. Rodewald H-R, 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.
23. Nishikawa S, Kusakabe M, Yoshinaga K, Ogawa M, Hayashi S, Kunisada T, Era T, Sakakura T, Nishikawa S. In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development. EMBO J. 10:1991;2111-2118.
24. of special interest Takeda S, Shimizu T, Rodewald H-R. Interactions between c-kit and stem cell factor are not required for B cell development in vivo. Blood. 89:1997;518-525 This paper describes the potential of c-kit-deficient (W/W) early fetal liver progenitors to seed the host bone marrow and give rise to normal numbers of immature and mature B cells upon intravenous transfer into recombination-activating gene (RAG)-deficient recipient mice. In contrast, c-kit-deficient stem cells failed to compete against the RAG-deficient host cell to populate the early thymocytes compartments.
25. Broudy VC. Stem cell factor and hematopoiesis. Blood. 90:1997;1345-1364.
26. Kinashi T, Escobedo JA, Williams LT, Takatsu K, Springer TA. Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3 kinase and phospholipase C-gamma 1 pathways. Blood. 86:1995;2086-2090.
27. Serve H, Yee NS, Stella G, Sepp-Lorenzino L, Tan JC, Besmer P. Differential roles of P13-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO J. 14:1995;473-483.
28. Asamoto H, Mandel TE. Thymus in mice bearing the steel mutation : Morphologic studies on fetal, neonatal, organ-cultured, and grafted fetal thymus. Lab Invest. 45:1981;418-426.
29. Godfrey DI, Zlotnik A, Suda T. Phenotypic and functional characterisation of c-kit exprssion during intrathymic T cell development. J Immunol. 149:1992;2281-2285.
30. Morrissey PJ, McKenna H, Widmer MB, Braddy S, Voice R, Charrier K, Williams DE, Watson JD. Steel factor (c-kit ligand) stimulates the in vitro growth of immature CD3-/CD4-/CD8- thymocytes: synergy with IL-7. Cell Immunol. 157:1994;118-131.
31. Yee NS, Paek I, Besmer P. Role of kit-ligand in proliferation and suppression of apoptosis in mast cells: basis for radiosensitivity of white spotting and steel mutant mice. J Exp Med. 179:1994;1777-1787.
32. Brannan CI, Bedell MA, Resnick JL, Eppig JJ, Handel MA, Williams DE, Lyman SD, Donovan PJ, Jenkins NA, Copeland NG. Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail. Genes Dev. 6:1992;1832-1842.
33. Okura M, Maeda H, Nishikawa S, Mizoguchi M. Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice. J Invest Dermatol. 105:1995;322-328.
34. Brandt JE, Bhalla K, Hoffman R. Effects of interleukin-3 and c-kit ligand on the survival of various classes of human hematopoietic progenitor cells. Blood. 83:1994;1507-1514.
35. Mekori YA, Oh CK, Metcalfe DD. The role of c-Kit and its ligand, stem cell factor, in mast cell apoptosis. Int Arch Allergy Immunol. 107:1995;136-138.
36. Iemura A, Tsai M, Ando A, Wershil BK, Galli SJ. The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol. 144:1994;321-328.
37. Lee JW, Gersuk GM, Kiener PA, Beckham C, Ledbetter JA, Deeg HJ. HLA-DR-triggered inhibition of hemopoiesis involves Fas/Fas ligand interactions and is prevented by c-kit ligand. J Immunol. 159:1997;3211-3219.
38. Carson WE, Haldar S, Baiocchi RA, Croce CM, Caligiuri MA. The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci USA. 91:1994;7553-7557.
39. Strasser A, Harris AW, Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 67:1991;889-899.
40. - onwards.
41. Matthews W, Jordan CT, Wiegand GW, Pardoll D, Lemischka IR. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 65:1991;1143-1152.
42. Rosnet O, Marchetto S, DeLapeyriere O, Birnbaum D. Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. Oncogene. 6:1991;1641-1650.
43. Mackarehtschian K, Hardin JD, Moore KA, Boast S, Goff SP, Lemischka IF. Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity. 3:1995;147-161.
44. Moore TA, Zlotnik A. Differential effects of Flk-2/Flt-3 ligand and stem cell factor on murine thymic progenitor cells. J Immunol. 158:1997;4187-4192.
45. Sugamura K, Asao H, Kondo M, Tanaka N, Ishi N, Nakamura M, Takeshita T. The common gamma-chain for multiple cytokine receptors. Adv Immunol. 59:1995;225-277.
46. DiSanto JP, Kühn R, Müller W. Common cytokine receptor γ chain (γc)-dependent cytokines: understanding in vivo function by gene targeting. Immunol Rev. 148:1995;19-34.
47. Leonhard WJ, Shores EW, Love PE. Role of the cytokine receptor γ chain in cytokine signaling and lymphoid development. Immunol Rev. 148:1995;97-114.
48. Sudo T, Nishikawa S, Ohno N, Akiyama N, Tamakoshi M, Yoshida H, Nishikawa S. Expression and function of the interleukin 7 receptor in murine lymphocytes. Proc Natl Acad Sci USA. 90:1993;9125-9129.
49. Era T, Nishikawa S, Sudo T, Wang FH, Ogawa M, Kunisada T, Hayashi S-I, Nishikawa S-I. How B-precursor cells are driven to cycle. Immunol Rev. 137:1994;35-51.
50. Kondo M, Ohashi Y, Tada K, Nakamura M, Sugamura K. Expression of the mouse interleukin-2 receptor gamma chain in various cell populations of the thymus and spleen. Eur J Immunol. 24:1994;2026-2030.
51. of outstanding interest Orlic D, Girard LJ, Lee D, Anderson SM, Puck JM, Bodine DM. Interleukin-7Rα mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors. Exp Hematol. 25:1997;217-222 This paper reports the analysis of IL-7 receptor (IL-7R)α and γχ chain expression in murine multipotent hematopoietic stem cells (HSCs) and early lymphoid precursors. Whereas the γc chain is expressed in HSCs, immature lymphocytes and mature T and B cells, the IL-7Rα chain is not found in HSCs, although it is strongly expressed in lymphoid precursors. These data are consistent with the hypothesis that expression of the IL-7Rα chain in hematopietic precursors marks commitment to the lymphoid lineage.
52. Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature. 333:1988;571-573.
53. Watson JD, Morrissey PJ, Namen AE, Conlon PJ, Widmer MB. Effect of IL-7 on the growth of fetal thymocytes in culture. J Immunol. 143:1989;1215-1222.
54. Murray R, Suda T, Wrighton N, Lee F, Zlotnik A. IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int Immunol. 1:1989;526-531.
55. 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.
56. of special interest Moore TA, Von Freeden-Jeffry U, Murray R, Zlotnik A. Inhibition of gamma delta T cell development and early thymocyte maturation in IL7 -/- mice. J Immunol. 157:1996;2366-2373 This paper, together with [58,59] reports the selective absence of γδ T-cell development in mice deficient in IL-7 receptor/IL-7 signaling. In contrast, αβ T cells develop (albeit in reduced numbers) in these mice, pointing to a differential cytokine dependency for these two T-cell lineages.
57. +) thymocytes in normal and genetically modified mice. J Immunol. 154:1995;5103-5113.
58. of special interest Maki K, Sunaga S, Komagata Y, Kodaira Y, Mabuchi A, Karasuyama H, Yokomuro K, Miyazaki JI, Ikuta K. Interleukin 7 receptor-deficient mice lack γδ T cells. Proc Natl Acad Sci USA. 93:1996;7172-7177 This paper, together with [56,59] reports the selective absence of γδ T-cell development in mice deficient in IL-7/IL-7R signaling. In contrast, αβ T cells develop (albeit in reduced numbers) in these mice, pointing to a differential cytokine dependency for these two T-cell lineages.
59. of special interest He YW, Malek TR. Interleukin-7 receptor α is essential for the development of γδ + T cells, but not natural killer cells. J Exp Med. 184:1996;289-293 This paper, together with [56,58] reports the selective absence of γδ T-cell development in mice deficient in IL-7/IL-7R signaling. In contrast, αβ T cells develop (albeit in reduced numbers) in these mice, pointing to a differential cytokine dependency for these two T-cell lineages.
60. of outstanding interest 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. Cell. 89:1997;1011-1019 A series of papers, with [77,78,80] suggesting that enforced expression of human Bcl-2 could rescue T-cell development in IL-7 receptor (IL-7R)α- or γc-deficient mice. In IL-7Rα-/- mice, αβ T-cell development was clearly enhanced by constitutive Bcl-2 expression, in terms of cellularly and peripheral T-cell function. Curiously, the Bcl-2 transgene did not rescue γδ T cells in IL-7Rα-deficient mice, and no effects on B-cell development were observed.
61. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Siegler 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.
62. 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.
63. DiSanto JP, Müller 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.
64. Ohbo K, Suda T, Hashiyama M, Mantani A, Ikebe M, Miyakawa K, Moriyama M, Nakamura M, Katsuki M, Takahashi K, et al. Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. Blood. 87:1996;956-967.
65. He YW, Nakajima H, Leonhard WJ, Adkins B, Malek TR. The common γ-chain of cytokine receptors regulates intrathymic T cell development at multiple stages. J Immunol. 158:1997;2592-2599.
66. of special interest Lantz O, Sharara LI, Tilloy F, Andersson Å, DiSanto JP. Lineage relationships and differentiation of NK T cells: intrathymic selection and IL-4 production in the absence of NKR-P1 and Ly49 molecules. J Exp Med. 185:1997;1395-1401 This paper reports the development of natural killer (NK)-T cells in common cytokine receptor γ chain (γc)-deficient mice. Using a sensitive PCR approach to detect the invariant T-cell receptor Vα14 chain, intrathymically NK-T cells were identified in these mice, which produced IL-4 when cultured with thymic stromal cell-derived lymphopoietin in vitro. In contrast, peripheral NK-T cells were absent. These results suggest that NK-T cells can develop in the absence of γc, but that their peripheral maintenance is γc-dependent. This paper also demonstrates that thymic stromal cell-derived lymphopoietin can function in a γc-independent fashion.
67. -/- mice, in which both of these lymphoid cell types are normally present. Taken together, these data support the idea that IL-15 may be critical for the development of thymus-independent T/NK cells (see also [69].
68. Schimpl A, Hünig T, Elbe A, Berberich I, Krämer S, Merz H, Feller AC, Sadlack B, Schorle H, Horak I, Ohashi PS. Development and function of the immune system in mice with targeted disruption of the interleukin 2 gene. Bluethmann H. Transgenesis and Targeted Mutagenesis in Immunology. 1994;191-202 Academic Press, San Diego.
69. DiSanto JP. Cytokines: shared receptors, distinct functions. Curr Biol. 7:1997;424-426.
70. + cell development. J Immunol. 159:1997;5931-5935.
71. + B cells and produces a novel growth factor affecting B and T lineage cells. Exp Hematol. 22:1994;321-328.
72. Boise LH, Minn AJ, June CH, Lindsten T, Thompson CB. Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division. Proc Natl Acad Sci USA. 92:1995;5491-5495.
73. Akbar AN, Borthwick NJ, Wickremasinghe RG, Panayoitidis P, Pilling D, Bofill M, Krajewski S, Reed JC, Salmon M. Interleukin-2 receptor common gamma-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: selective induction of anti-apoptotic (bcl-2, bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene expression. Eur J Immunol. 26:1996;294-299.
74. of special interest Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai CF, Croce CM, Baumann H, Caligiuri MA. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest. 99:1997;937-943 This report demonstrates that NK cells express transcripts for the IL-15Rα chain and that picomolar concentrations of IL-15 can sustain NK survival vitro for a prolonged period (8 days) in the absence of serum. The mechanism of the IL-15 effect appears in part through the maintenance of Bcl-2 levels.
75. Vella A, Teague TK, Ihle J, Kappler J, Marrack P. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4. J Exp Med. 186:1997;325-330.
76. + stage. The authors define a critical transition point prior to T-cell receptor rearrangements, where IL-7 signaling influence thymocyte cell survival and proliferation.
77. -/- mice, αβ T-cell development was clearly enhanced by constituitive Bcl-2 expression, in terms of cellularity and peripheral T-cell function. Curiously, the Bcl-2 transgene did not rescue γδ T cells in IL-7Rα-deficient mice, and no effects on B-cell development were observed.
78. - mice. Here, in contrast to [80], Kondo et al. found an increase in thymic cellularity and in the number of αβ T cells in bcl-2 transgenic mice.
79. Nakayama K, Nakayama K, Dustin LB, Loh DY. T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice. J Exp Med. 182:1995;1101-1109.
80. - mice. A possible explanation for the differences between the findings in these papers would be that any observed effects of the Bcl-2 transgene are related to T-cell accumulation rather than a major role for IL-7Rα/γc signaling via Bcl-2 in enhancing lymphocyte survival.
81. of special interest Candeias S, Muegge K, Durum SK. IL-7 receptor and VDJ recombination: trophic versus mechanistic actions. Immunity. 6:1997;501-508 A recent review examining the role of IL-7 mediated signals in T-cell receptor (TCR) recombination in attempt to define whether IL-7 acts primarily as a trophic factor for early thymocytes or is directly involved in the process of TCR rearrangements.
82. of special interest Maki K, Sunuga S, Ikuta K. The V-J recombination of T cell receptor-γ genes is blocked in interleukin-7 receptor-deficient mice. J Exp Med. 184:1996;2423-2427 One of a series of papers (with [83,84]) which analyse TCR recombination in mice deficient in IL-7Rα in order to determine why γδ T-cell development is blocked in these mice. Here Maki et al. find normal levels of TCRδ and TCRβ rearrangements but no rearrangements at the TCR γ loci.
83. of special interest Candeias S, Peschon JJ, Muegge K, Durum SK. Defective T-cell receptor gamma gene rearrangement in interleukin-7 receptor knockout mice. Immunol Lett. 57:1997;9-14 One of a series of papers (with [82,84]) which analyse TCR recombination in mice deficient in IL-7Rα in order to determine why γδ T-cell development is blocked in these mice. Candeias et al. (here) and Perumal et al. [84] find reduced but detectable TCR-γ rearrangements, unlike [82].
84. of special interest Perumal NB, Kenniston T Jr, Tweardy DJ, Dyer KF, Hoffman R, Peschon J, Appasamy PM. TCR-gamma genes are rearranged but not transcribed in IL-7R alpha-deficient mice. J Immunol. 158:1997;5744-5750 One of a series of papers (with [82,83]) which analyse T-cell receptor (TCR) recombination in mice deficient in IL-7 receptor (IL-7R)α in order to determine why γδ T-cell development is blocked in these mice.
85. - mice. In contrast, junctional diversity of TCR γ and δ rearrangements was comparably diverse (polyclonal) in γc-deficient and in wild-type thymocytes (see also annotation [82,83,84]).
86. - thymocytes. In order to determine whether the abnormal TCR γ levels were the cause of blocked γδ T-cell development in these mice, the authors introduced productively rearranged TCR γ or TCR γδ transgenes into γc-deficient mice. The expression of γδ transgenes failed to restore γδ T-cell development to normal levels in the absence of γc, thereby ruling out a mechanistic defect in the TCR rearrangement process. These data suggest that signals through γc-containing receptors may be essential for the survival of γδ T cells.
87. Crompton T, Outram SV, Buckland J, Owen MJ. A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor alpha chain-deficient mice. Eur J Immunol. 27:1997;100-104.
88. DiSanto JP, Guy-Grand D, Fisher A, Tarakhovsky A. Critical role for the common cytokine receptor gamma chain in intrathymic and peripheral T cell selection. J Exp Med. 183:1996;1111-1118.
89. Grawunder U, Winkler TH, Melchers F. Regulation of recombination activating gene expression during lymphocyte development. Curr Top Microbiol Immunol. 217:1996;31-43.
90. Desiderio S, Lin WC, Li Z. The cell cycle and V(D)J recombination. Curr Top Microbiol Immunol. 217:1996;45-59.
91. Rolink A, Grawunder U, Haasner D, Strasser A, Melchers F. Immature surface Ig+ B cells can continue to rearrange kappa and lambda L chain gene loci. J Exp Med. 178:1993;1263-1270.
92. -/- thymi are essentially alymphoid, demonstrating that these two signaling pathways are essential for the development of the earliest thymic precursors. Morever, these results suggest that tyrosine kinase and JAK-STAT pathways compensate for each other in T-cell development in vivo. The paper also shows that γc-associated cytokine receptors are not critical for hematopoietic stem cell function (i.e., myelopoiesis and erythropoiesis) in c-kit deficient mice.
93. Rodewald H-R, Kretzschmar K, Takeda S, Hohl C, Dessing M. Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J. 13:1994;4229-4240.
94. Carding SR, Kyes S, Jenkinson EJ, Kingston R, Bottomly K, Owen JJT, Hayday AC. Developmentally regulated fetal thymic and extrathymic T-cell receptor γδ gene expression. Genes Dev. 4:1990;1304-1315.
95. Carlsson L, Overmo C, Holmberg D. Developmentally controlled selection of antibody genes: characterization of individual VH7183 genes and evidence for stage-specific somatic diversification. Eur J Immunol. 22:1992;71-78.
96. 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.
97. Benoist C, Mathis D. Selection for survival? Science. 276:1997;2000-2001.
98. + T cells from IL-7-deficient mice have a normal distribution and selection but exhibit impaired cytokine production. Int Immunol. 8:1996;1759-1766.
99. Boesteanu A, Silva ADD, Nakajima H, Leonard WJ, Peschon JJ, Joyce S. Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development. J Exp Med. 186:1997;331-336.