1998 Fiscal Year Final Research Report Summary
Analysis of lymphpcyte differentiation and growth mechanism by IL-7 receptor deficient mice
| Project/Area Number |
09836005
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
免疫の制御機構
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
IKUTA Koichi Kyoto university Graduate School of Medicine Associate Professor, 医学研究科, 助教授 (90193177)
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| Project Period (FY) |
1997 – 1998
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| Keywords | IL-7 receptor / Bcl-2 / gammadelta T cell / transgenic mouse |
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| Research Abstract |
IL-7 receptor (IL-7R)-deficient mice have severely impaired expansion of early lymphocytes and lack gammadelta T cells. In addition, the V-J recombination of TCR gamma genes is blocked in these mutant mice. To test the role of IL-7R on expansion and/or survival of gammadelta T cells irrespective of the recombination, we introduced a Vgamma2/Vdelta5 transgene into the IL-7R-deficient mice. More than 70% of thymocytes were transgenic gammadelta T cells in Vgamma2 Tg+ IL-7R+/- mice. In contrast, gammadelta T cells were not detected in the thymus of Vgamma2 Tg+ IL-7R-/- mice. In addition, no distinct gammadelta T-cell population was observed in Vgamma2 Tg+ IL- 7R-/- spleen. These data demonstrated that IL-7R is crucial for the expansion and/or survival of gammadelta T cells in the thymus and spleen. To examine the extrathymic gammadelta T-cell development, we next analyzed intraepithelial lymphocytes (IEL) in the small intestine. Cell numbers of gammadelta T cells were partially restored in the small intestine of IL-7R-/- mice by introduction of the transgene. These data demonstrated that IL-7R is dispensable for the expansion and/or survival of gammadelta IEL in the intestine and that some other cytokine like IL-15 can complement IL-7 to support extrathymic gammadelta T-cell development.
It has been reported that the introduction of Bcl-2 transgenes restore alphabeta T cell development in IL-7R-deficient mice. However, this did not restore gammadelta T cell development in Vgamma2 Tg+ IL-7R-/- mice. These results suggested that IL-7R signaling plays a role in the proliferation of gammadelta T cells as well as their survival.
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