Analysis and outlining the regulation of rejection responses in cardiac xenotransplantation

供体器官短缺是心脏移植领域一个严重而持续存在的问题。缓解这种情况的一种方法是开发一个可行的异种供体器官计划，利用密切相关的和谐供体，这揭示了细胞排斥反应。然而，协调异种移植排斥反应中存在的细胞机制类型尚不清楚，并且没有精确的报告概述异种移植中细胞排斥反应的调节。我们的研究旨在：a)分析哪些辅助性T淋巴细胞（Th）可能对异种移植物的一致性排斥反应有影响；b)确定细胞如何识别异种抗原。我们研究了在小鼠抗大鼠物种组合中是否诱导了受MHC限制的CD4^+和CD8^+ T细胞。在小鼠抗大鼠混合淋巴细胞反应（MLRs）中，除自身抗原呈递细胞（APC）限制CD4^+ Th外，还诱导了xene APC限制CD4^+和CD8^+ Th。利用这些MLRs建立了Th克隆的两种表型（CD4^+和CD8^+）。每个克隆均用大鼠APC单独刺激。CD8+ Th克隆为ⅰ类MHC限制性大鼠，CD4+ Th克隆为ⅱ类MHC限制性大鼠。我们的研究结果可能为临床近缘种异种移植诱导的细胞免疫反应提供重要的见解。

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.