| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Keisuke Medical School, Osaka City University, Associate Prof., 医学部, 助教授 (70137230)
WADA Seiji Medical School, Osaka City University, Associate Prof, 医学部, 講師 (20158695)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Second-set rejection is generally regarded as a phenomenon mainly mediated by humoral cytotoxic antibodies, although a few discordant data have been presented. In the reported experiments, we have taken advantage of the absence of production of specific cytotoxic alloantibodies contrasting with normal development of transplantation cellular immunity, in 2 models of animals the recombination activation gene deletion (RAG) mice wich are fully defective in any functionnal T cell and B cell, and the chimeric (BALB/c * CBA) mice. Anti-B cytotoxic antibodies were not detectable in any of hyperimmunized chimeric mice, yet accelerated rejection of B6 skin transplant occurred : graft survival of 8.6 * 0.5 days (d), comparable to the 8.9 * 0.8 d survival in CBA control mice subjected to the same hyperimmunization procedure, and significantly shorter than in non-hyperirnmunized (BALB/c CBA) chimeras (11.6 * 0.5 d) or in non-hyperimmunized CBA control mice (12.1 * 0.6 d). High titers of anti-B6 cy
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totoxic antibodies were present in the serum of hyperimmunized CBA control mice. Transfer experiments were carried out. The recipient mice were then grafted with B6 skin. The graft survival was over 14 d in mice treated with irradiation alone, with irradiation + serum, or with irradiation + CD4+ T cells. It was significantly shorter in mice treated with irradiation + whole spleen cells, with irradiation + T cells, or with irradiation +CD8+ T cells (8.9 * 0.8 d). When RAG mice recieved pre-sensitesed [TCD4+ or TCD8+ or T cells] or serum from hyperinununised B6 mice, accelerated rejection of the skin grafts was occured only in the groups of mice injected with sensitesed TCD8+ cells or T cells (12.0 * 0.68 d and 14.0 * 0.84 d) respectively this delay is longuer in mice injected with TCD4+ cells (16.5 * 0.11d) The latter cells have been able to transfer the property of inducing accelerated rejection into naive mice. T cells, and especially the CD8+ subset, thus appear to be responsible for the second-set rejection in the absence of anti-donor antibodies, in the model of chimeric mice. These sensitized CD8+ T cells are likely to also play an important role in normal mice. Less
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