Role of indirect allorecognition in experimental late acute rejection.
Role of indirect allorecognition in experimental late acute rejection.
复制标题
间接同种异体识别在实验性晚期急性排斥反应中的作用。
DOI：
10.1097/00007890-199712270-00033
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Sayegh,MH
中科院分区：
文献类型：
--
作者：
Vella,JP;Vos,L;Carpenter,CB;Sayegh,MH
背景：晚期急性排斥反应影响高达28%的肾移植受者，并且仍然是晚期移植物丢失的主要危险因素。由于供体来源的抗原呈递细胞随时间耗尽，由自身抗原呈递细胞呈递的供体来源的同种异体抗原肽的T细胞识别（同种异体识别的“间接途径”）可能在晚期急性排斥发作的起始中起关键作用。方法：为了检验这一假设，我们开发了一个临床相关的大鼠实验模型，（Wistar-Furth/刘易斯），其中同种异体移植物接受者在移植后接受环孢霉素1个月，然后在停止免疫抑制后允许移植物排斥。此时，对供体来源的合成II类MHC同种异体肽以及完整供体（Wistar-Furth）细胞进行淋巴细胞增殖试验。研究的效应机制包括迟发型超敏反应（DTH）的反应，淋巴细胞介导的细胞毒性，和同种抗体production.Results.Lymphocytes受体进行晚期急性排斥反应有显着抑制混合淋巴细胞反应增殖完整的供体细胞。然而，引起了供体来源的25-mer多态性II类MHC同种异体肽的显著增殖。在体内，观察到显着的DTH反应的MHC同种异体肽和完整的Wistar-Furth细胞。外周血淋巴细胞也表现出显着的杀伤供体细胞，虽然不是第三方细胞，和抗供体同种异体抗体检测通过流式细胞术。结论。我们的研究结果表明，通过间接途径引发的T细胞是存在于急性排斥反应发生后，停止环孢霉素。此时混合淋巴细胞反应性明显降低。此外，在这种同种异体肽致敏的T细胞与特异性DTH应答的引发和向B细胞提供帮助以产生同种异体抗体和活化CD 8 + T细胞以成为效应细胞毒性细胞之间存在关联。
Background.Late acute rejection affects up to 28% of renal allograft recipients and remains a major risk factor for late graft loss. As donor-origin antigen-presenting cells are depleted with time, T-cell recognition of donor-derived alloantigenic peptides presented by self antigen-presenting cells (the “indirect pathway” of allorecognition) may play a key role in the initiation of late acute rejection episodes.Methods.To test this hypothesis, we developed a clinically relevant experimental model in the rat (Wistar-Furth/Lewis) in which allograft recipients received cyclosporine for 1 month after transplantation and were then allowed to reject the graft upon discontinuation of immunosuppression. Lymphocyte proliferation assays to synthetic class II MHC allopeptides of donor origin and also to intact donor (Wistar-Furth) cells were performed at this time. The effector mechanisms studied included delayed-type hypersensitivity (DTH) responses, lymphocyte-mediated cytotoxicity, and alloantibody production.Results.Lymphocytes from recipients undergoing late acute rejection had marked suppression of mixed lymphocyte reaction proliferation to intact donor cells. Significant proliferation to donor-derived 25-mer polymorphic class II MHC allopeptides was elicited, however. In vivo, significant DTH responses were observed to both MHC allopeptides and intact Wistar-Furth cells. Recipient lymphocytes also exhibited significant killing of donor cells, although not third-party cells, and anti-donor alloantibodies were detected by flow cytometry.Conclusion.Our results indicate that T cells primed via the indirect pathway are present during acute rejection that occurs after discontinuation of cyclosporine. Mixed lymphocyte reactivity is markedly reduced at this time. Furthermore, there is an association between such allopeptide-primed T cells and the elicitation of specific DTH responses and provision of help to B cells to produce alloantibodies and activation of CD8+ T cells to become effector cytotoxic cells.