1993 Fiscal Year Final Research Report Summary
Tolerance induction of alloreactive T cells and regulation of graft rejection
| Project/Area Number |
04454207
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIWARA Hiromi Osaka Univ.Med.Sch.Assoc.Prof., 医学部, 助教授 (70116094)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUGI Atsushi Res.Development Cosp of Japan, 研究者
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| Project Period (FY) |
1992 – 1993
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| Keywords | tolerance / transplantation immunology / helper T cells / DST / immunosuppresive drugs |
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| Research Abstract |
One of major issues in transplantation immunology is to develop methods to regulate allograft responses. This study investigated an approach to regulate allograft responses by either a single DST(donor-specific transfusion), repeated administrasion of immunosuppressive drugs (FK506 or rapamycin) or the combination of these. The follwing were revealed : (1)Allo class 1 MHC-reactive helper T cells (Th) consist of (a)CD4^+ and CD8^+ Th with the capacity to produce high levels of IL-2 and (b) CD4^+ Th with the limited capacity of IL-2 production. The former is susceptible to donor-specific transfusion (DST) and rendered easily tolerant by a single DST, whereas the latter is DST-resistant. (2)In the donor-host combination involving the DSP-susceptible and DST-resistant Th subsets, the induction and maintenance of tolerance of the former is inhibited by the operation of the DSP-resistant subset, indicating the modulation of allograft responses based on cellular interactions. (3)It was found that FK506 or rapamycin at suboptimal deses was effective for suppressing allograft rejection responses by the combination with a single DST under which either of these treatments alone failed to inhibit rejection responses. Thus, by presenting a practical approach for producing a beneficial effect on immunomodulation of allograft responses using DST and by demonstrating cellular mechanisms underlying such an immunomodulation, the present study may provide a significant contribution to transplantation immunology.
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