IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지

Interleukin-7 Receptor is Indispensable for Proliferation and Survival in Thymic ${\gamma}{\delta}$T Cell Development

  • Kim, Dong-Hyun (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Yoon, Byung-Hak (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Jung, Joo-Eun (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Kim, Hoog-Sook (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Ko, Seong-Hee (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Choi, Eun-Young (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Lee, Kwang-Ho (Bio-Food and Drug Research Center, and Department of Biotechnology, Faculty of Life Science, College of Natural Science, Konkuk University) ;
  • Kim, Kyung-Jae (Department of Pharmacy, Sahmyook University) ;
  • Ye, Sang-Kyu (Department of Pharmacology, Seoul National University College of Medicine) ;
  • Chung, Myung-Hee (Department of Pharmacology, Seoul National University College of Medicine)
  • Published : 2005.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

Keywords

References

  1. Hayday AC: ${\gamma}{\delta}$cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18; 975-1026, 2000 https://doi.org/10.1146/annurev.immunol.18.1.975
  2. Leonard WJ, O'Shea JJ: Jaks and STATs: biological implications. Annu Rev Immunol 16;293-322, 1998 https://doi.org/10.1146/annurev.immunol.16.1.293
  3. Park LS, Martin U, Garka K, Gliniak B, Di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG, Ziegler SF, Morrissey PJ, Paxton R, Sims JE: Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 192;659-670, 2000 https://doi.org/10.1084/jem.192.5.659
  4. Bhatia SK, Tygrett LT, Grabstein KH, Waldschmidt TJ: The effect of in vivo IL- 7 deprivation on T cell maturation. J Exp Med 181;1399-1409, 1995 https://doi.org/10.1084/jem.181.4.1399
  5. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL: Early lymphocyte expansion is severely impaired in interleukin-7 receptor-deficient mice. J Exp Med 180;1955-1960, 1994 https://doi.org/10.1084/jem.180.5.1955
  6. Maki K, Sunaga S, Kodaira Y, Mabuchi A, Karasuyama H, Yokomuro K, Miyazaki J, Ikuta K: Interleukin- 7 receptordeficient tnice lack ${\gamma}{\delta}T$ cells. Proc Natl Acad Sci USA 93;7172-7177, 1996
  7. He Y, Malek TR: Interleukin- 7 receptor $\alpha$ is essential for the development of ${\gamma}{\delta}$+ T cells, but not natural killer cells. J Exp Med 184;289-293, 1996 https://doi.org/10.1084/jem.184.1.289
  8. Candeias S, Muegge K, Durum SK: IL-7 receptor and VDJ recombination: trophic versus mechanistic actions. Immunity 6;501-508, 1997 https://doi.org/10.1016/S1074-7613(00)80338-6
  9. von Frecdcn-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. Immunity 7;147-154, 1997 https://doi.org/10.1016/S1074-7613(00)80517-8
  10. Akashi K, Kondo M, von Freeden-Jeffrv U, Murray R, Weissman IL: Bcl-2 rescues T lymphopoiesis in interleukin- 7 receptor-deficient mice. Cell 89;1033-1041, 1997 https://doi.org/10.1016/S0092-8674(00)80291-3
  11. Corcoran AE, Smart FM, Cowling RJ, Crompton T, Owen MJ, Venkitaraman AR: The interleukin- 7 receptor $\alpha$ chain transmits distinct signals for proliferation and differentiation during B lymphopoiesis. EMBO J 15;1924-1932, 1996
  12. Maraskovsky L, Teepe M, Morrissey PJ, Braddy S, Miller RE, Lynch DH, Peshon JJ: Impaired survival and proliferation in IL-7 receptor-deficient peripheral T cells. J Immunol 157; 5315-5323, 1996
  13. Corcoran AE, Riddell A, Krooshoop D, Venkitaraman AR: Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature 391;904-907, 1998 https://doi.org/10.1038/36122
  14. Maki K, Sunaga S, Ikuta K: The V-J recombination of T cell receptor-Ygenes is blocked in Interleukin-7 receptor-deficient mice. J Exp Med 184;2423-2427, 1996 https://doi.org/10.1084/jem.184.6.2423
  15. Ye SK, Maki K, Kitamura T, Sunaga S, Akashi K, Domen J, Weissman IL, Honjo T, Ikuta K: Induction of germline transcription in the TCR$\gamma$ locus by Stat5: implications for accessibility control by the IL- 7 receptor. Immunity 11 ;213223, 1999
  16. Giri JG., Kumaki S, Ahdied M, Friend DJ, Lootnis A, Shanebeck K, DuBose R, Cosman D, Park LS, Anderson DM: Identification and cloning of a novel IL-15 binding protein that is structurally related to the$\alpha$ chain of the IL-2 receptor. EMBO J 14:3654-3663. 1995
  17. Suzuki H, Duncan GS, Takimoto H, Mak TW: Abnormal development of intestinal lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor $\beta$ chain. J Exp Med 185;499-505, 1997 https://doi.org/10.1084/jem.185.3.499
  18. Porter BO, Malek TR: IL-2R beta/IL- 7R alpha doubly deficient mice recapitulate the thymic and intraepithelial lymphocyte (IEL) developmental defects of Y gamma c-/- mice: roles for both IL-2 and IL-15 in CD8 alpha alpha IEL development. J Immunol 163; 5906-5912, 1999
  19. Kondo M, Akashi K, Doment J, Sugamura K, Weissman IL: Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common g chain-deficient mice. Immunity 7;155-62, 1997 https://doi.org/10.1016/S1074-7613(00)80518-X
  20. Malissen M, Pereira P, Gerber DL Malissen B, DiSanto JP: The common cytokine receptor $\gamma$ chain controls survival of ${\gamma}{\delta}T$ cells. J Exp Med 186;1277-85, 1997 https://doi.org/10.1084/jem.186.8.1277
  21. Ye SK, Maki K, Lee HC, Ito A, Kawai K, Suzuki H, Mak TW, Chien YH, Honjo T, Ikuta K: Differential roles of cytokine receptors in the development of epidermal ${\gamma}{\delta}T$ cells. J Immunol 167; 1929-1934, 2001 https://doi.org/10.4049/jimmunol.167.4.1929
  22. Domen J, Gandy KL, Weissman IL: Systemic overexpression of Bcl-2 in the hematopoietic system protects transgenic mice from the consequences of lethal irradiation. Blood 91;2272-2282, 1998
  23. Ishida I, Verbeek S, Bonneville M, Itohara S, Berns A, Tonegawa S: T-cell receptor ${\gamma}{\delta}$ and $\gamma$ transgenic mice suggest a role of a g gene silencer in the generation of ${\alpha}{\beta}T$ cells. Proc Natl Acad Sci USA 87;3067-3071, 1990
  24. Ito K, Van Kaer L, Bonneville M, Hsu S, Murohy DB, Tonegawa S: Recognition of the product of a novel MHC TL region gene (27b) by a mouse ${\gamma}{\delta}T$ cell receptor. Cell 62;549-561, 1990 https://doi.org/10.1016/0092-8674(90)90019-B
  25. Ishikawa H, Li Y, Abeliovich A, Yamamoto S, Kaufinann HH, Tonegawa S: Cytotoxic and interferonv-producing activities of ${\gamma}{\delta}T$ cells in the mouse intestinal epithelium are strain dependent. Proc Natl Acad Sci USA 90;8204-8208, 1993
  26. Bonneville M, Ishida I, Mombaerts P, Katsuki M, Verbeek S, Berns A, Tonegawa S: Blockage of ${\alpha}{\beta}T$-cell development by $TCR{\gamma}{\delta}$ transgenes. Nature 342;931-934, 1989 https://doi.org/10.1038/342931a0
  27. Di SantoJP, Aifantis I, Rosmaraki E, Garcia C, Feinberg J, FeWing HJ, Fischer A, von Boehmer H, Rocha B: The common cytokine receptor Y chain and the pre- T cell receptor provide independent but critically overlapping signals in early ${\alpha}{\beta}T$ cell development. J Exp Med 189;563-574, 1999 https://doi.org/10.1084/jem.189.3.563