Tolerance induction of alloantigen-reactive T cells and analysis of its immunologic and cell-biologic mechanisms

本课题旨在（1）确定诱导辅助/DTH型T细胞对同种抗原反应性耐受的条件，（2）分析耐受的免疫学和细胞生物学机制，发现：（1）门静脉输注同种异体细胞可导致对同种抗原反应性DTH T细胞的高度耐受。（2）上述耐受是通过a）抑制细胞活性的诱导、B）抗独特型抗体的产生和c）同种反应性DTH T细胞的克隆性消除介导和/或维持的;（3）同种异体I类H-2反应性Lyt-2^+辅助性T细胞通过用相应的同种异体细胞进行单次静脉内预致敏而变得耐受。这种耐受诱导既不需要用神经氨酸酶处理同种异体细胞，也不需要通过门静脉途径注射。实验结果还表明，同种异体I类H-2异种皮肤移植物在耐受受者中存活时间延长，为消除同种异体反应性和延长同种异体皮肤移植物存活时间提供了新的途径。

This project aimed to (1) define conditions which induce the tolerance of helper/DTH type of T cells reactive to allo-antigens and (2) analyze immunologic and cell-biologic mechanisms underlying the tolerance.We have found that: (1) the portal-venous adminiztration of allogeneic cells results in profound tolerance of alloantigen-reactive DTH T cells. The tolerance of these T cells was also inducible by i.v. administration of neuraminidase-treated allogeneic cells; (2) The above tolerance was mediated and/or maintained by a) induction of suppressor cell activity, b) generation of anti-idiotypic antibody and c) clonal elimination of alloreactive DTH T cells; (3) allo-class I H-2 reactive Lyt-2^+helper T cells were rendered tolerant by a single i.v. pre-sensitization with the corresponding allogeneic cells. This tolerance induction did neither require the treatment of allo-geneic cells with neuraminidase nor the injection via the portal venous route. It was also demonstrated that the prolonged survival of allo-class I H-2-disparate skin grafts was observed in such tolerant recipients.These results provide approaches to eliminate alloreactivity and to attempt the prolongation of allograft survival.