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

同种异体抗原反应性T细胞的耐受诱导及其免疫学和细胞生物学机制分析

• 批准号: 62480165
• 负责人: FUJIWARA Hiromi
• 金额: $ 4.48万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480165/
• 关键词: Transplantation immunity; immunologic tolerance; helper T cells; clonal deletion; ヘルパー型T細胞; asialogly coprotein receptor

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.

该项目旨在 (1) 确定诱导辅助/DTH 型 T 细胞对同种异体抗原反应的耐受性的条件，以及 (2) 分析耐受性背后的免疫学和细胞生物学机制。我们发现：(1) 同种异体细胞的门静脉给药导致对同种异体抗原反应性 DTH T 细胞的深度耐受。这些 T 细胞的耐受性也可通过静脉注射诱导。施用经神经氨酸酶处理的同种异体细胞； (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细胞的克隆消除来介导和/或维持的； (3) 同种异体 I 类 H-2 反应性 Lyt-2^+ 辅助 T 细胞通过单次静脉注射即可耐受。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处理同种异体细胞，也不需要通过门静脉途径注射。还证明，在此类耐受受体中观察到同种异体 I 类 H-2 不同皮肤移植物的存活时间延长。这些结果提供了消除同种异体反应性并尝试延长同种异体移植物存活的方法。

项目成果

Qian,J-h.: Transplantation. 43. 538-543 (1987)

钱建华：移植。

Sato, S.; Qian, J-h.; Kokudo, S.; Ikegami, R.; Suda, T.; Hamaoka, T.; Fujiwara, H.: "Studies on the induction of tolerance to alloantigens. III. Induction of antibodies directed against alloantigenspecific delayed-type-hypersensitivity T cells by a single

佐藤，S.；

Mizushima,Y.;et al.: J.Biochemistry. 102. 1193-1201 (1987)

Mizushima，Y.；等人：J.Biochemistry。

Sato,S.;et al.: J.Immunol.140. 717-722 (1988)

Sato，S.；等人：J.Immunol.140。

Sano, S.; Suda, T.; Qian, J-h.; Sato, S.; Ikegami, R.; Hamaoka, T.; Fujiwara, H.: "Abrogation of the capacity of delayed-type-hyper-sensitivity responses to alloantigens by intravenous injection of neuraminidase-treated allogeneic cells." J. Immunol.139.

萨诺，S.；