Analysis and outlining the regulation of rejection responses in cardiac xenotransplantation

分析并概述心脏异种移植中排斥反应的调节

• 批准号: 07671459
• 负责人: HIROSE Hajime
• 金额: $ 1.6万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671459/
• 关键词: xenotransplantation; concordant; rejection response; T lymphocyte; major histocompatibility complex; antigen presenting cell; mixed lymphocyte reaction; helper T cell clone; 心臓移植; 拒絶反応; T細胞; 異種抗原; CD4; CD8; 異種抗原提示細胞; T細胞クローン; リンパ球混合培養; 主要

The shortage of donor organs poses a serious and ongoing problem in the field of cardiac transplantation. One manner of alleviating the situation is to develop a viable xenogeneic donor organ program utilizing closely-related concordant donor, which reveals cellular rejection responses. However, the types of cellular mechanisms that exist in rejection responses of concordant xenotransplantation are unclear and there has been no precise report outlining the regulation of cellular rejection responses in xenotransplantion.Our studies were designed to : a) analyze which helper T lymphocytes (Th) have a possible effect on concordant xenograft rejection responses ; and b) determine how Th cells recognize xenoantigens. We investigated whether or not xeno major histocompatibility complex (MHC) restricted CD4^+ and CD8^+ T cells are induced in the mouse anti-rat species combination. In addition to self antigen presenting cell (APC) (self class ll)- restricted CD4^+ Th, xene APC-restricted CD4^+ and CD8^+ Th were induced in mouse anti-rat mixed lymphocyte reactions (MLRs). Both phenotypes (CD4^+ and CD8^+) of Th clones were established from these MLRs. Each clone was stimulated exclusively by rat APC.CD8+ Th clones were rat class I MHC-restricted, and CD4+ Th clones were rat class ll MHC restricted.Our results may provide an important insight into the cellular immune responses induced by clinical xenotransplantation between closely-related species.

供体器官的短缺在心脏移植领域构成了严重和持续的问题。缓解这种情况的一种方式是开发一种可行的异种供体器官计划，利用密切相关的一致供体，这揭示了细胞排斥反应。然而，存在于一致性异种移植排斥反应的细胞机制的类型还不清楚，一直没有确切的报告概述了异种移植细胞排斥反应的调控，我们的研究旨在：a）分析辅助性T淋巴细胞（Th）有可能对一致性异种移植排斥反应的影响;和B）确定Th细胞如何识别异种抗原。我们研究了异种主要组织相容性复合体（MHC）限制性CD 4 ^+和CD 8 ^+ T细胞是否在小鼠抗大鼠种属组合中被诱导。在小鼠抗大鼠混合淋巴细胞反应（MLR）中，除了自身抗原呈递细胞（APC）（自身II类）限制性的CD 4 ^+ Th外，xene APC限制性的CD 4 ^+和CD 8 ^+ Th也被诱导。从这些MLR中建立了Th克隆的两种表型（CD 4 ^+和CD 8 ^+）。结果表明，大鼠APC特异性地刺激了CD 8 + Th细胞克隆和CD 4 + Th细胞克隆，其中CD 8 + Th细胞克隆为大鼠I类MHC限制性克隆，CD 4 + Th细胞克隆为大鼠II类MHC限制性克隆。

项目成果

Toshio Hirota, et al.: "Mouse CD4 and CD8 T-cellclones that recognize xeno-Antigens directly on xeno-Antigen presenting cellsin-xeno MHC-restricted ways." Transplantation proceedings. 29. 950-952 (1997)

Toshio Hirota 等人：“小鼠 CD4 和 CD8 T 细胞克隆可直接识别异种抗原，以异种 MHC 限制的方式呈递细胞。”

Toshio Hirota, et al.: "Direct recognition of rat MHC antigens on rat antigen-presenting cells by mouse CD4^+ and CD8^+ T cells and establishment of T cell clones exhibiting a direct recognition pathway." (in press).

Toshio Hirota 等人：“小鼠 CD4+ 和 CD8+ T 细胞直接识别大鼠抗原呈递细胞上的大鼠 MHC 抗原，并建立表现出直接识别途径的 T 细胞克隆。”

Toshio Hirota: "Evidence of direct recognition subset in xeno-reactive helper T cell" Artificial Organs. (1996)

Toshio Hirota：“异种反应辅助 T 细胞中直接识别子集的证据”人工器官。