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

本项目旨在(1)明确诱导同种异体抗原反应的辅助型/迟发型T细胞耐受的条件；(2)分析免疫耐受和细胞生物学机制。我们发现：(1)门静脉给药导致同种异体抗原反应型迟发型T细胞的深度耐受。静脉注射也可诱导这些T细胞的耐受性。(2)上述耐受性是通过a)抑制细胞活性的诱导，b)抗独特型抗体的产生和c)同种异体反应性DTH T细胞的克隆性消除而介导和/或维持的；(3)通过一次静脉注射使同种I型H-2反应性Lyt-2~+辅助性T细胞耐受。用相应的同种异体细胞进行预敏化。这种耐受诱导既不需要用神经氨酸酶治疗同种异体细胞，也不需要通过门静脉途径注射。研究还表明，在这种耐受的受者中，可以观察到I-H-2异种异体皮肤移植物的存活时间延长。这些结果为消除同种异体反应性和尝试延长同种异体移植物的存活时间提供了方法。

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.