Detection of minor alloantigen-specific cytotoxic T cells after rejection of murine orthotopic corneal allografts: evidence that graft antigens are recognized exclusively via the "indirect pathway".
Detection of minor alloantigen-specific cytotoxic T cells after rejection of murine orthotopic corneal allografts: evidence that graft antigens are recognized exclusively via the "indirect pathway".
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小鼠原位角膜同种异体移植物排斥后次要同种异体抗原特异性细胞毒性 T 细胞的检测：移植物抗原仅通过“间接途径”识别的证据。
DOI：
10.1097/00007890-199910150-00011
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发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Ksander,BR
中科院分区：
文献类型：
--
作者：
Sano,Y;Streilein,JW;Ksander,BR
背景：在正常眼移植床中同种异体角膜移植排斥反应的免疫机制尚未确定。这两种类型的移植物的受体和排斥显示供体特异性迟发性超敏反应和体外增殖的致敏T细胞，但都没有开发传统的，供体特异性细胞毒性T细胞。我们希望确定是否产生非常规的供体特异性细胞毒性T细胞在排斥小鼠，识别供体的受体主要组织相容性复合体（MHC）分子的次要同种异体抗原。方法。BALB/c小鼠接受原位角膜移植C57 BL/10捐助者在正常的眼睛。在4周时（当50%的移植物可以被指定为排斥时），在引流淋巴结和脾脏中的引发的细胞毒性T淋巴细胞（CTL）活性在选择用于在受体MHC分子上呈递供体型次要H抗原的靶标上进行测定。对照组小鼠接受异位角膜同种异体移植，并进行了类似的examined.Results. acetophoid器官的受体，拒绝原位或异位角膜同种异体移植包含CTL裂解表达供体型小H抗原的受体MHC分子提出的目标。相比之下，接受原位角膜移植的受者的淋巴细胞中没有检测到CTL活性。排斥原位角膜移植植入正常小鼠眼睛直接与供体特异性CTL的产生，识别未成年人H抗原的背景下，recipients MHC molecules.Conclusions.These结果表明同种异体抗原呈递的间接途径是唯一的途径操作的过程中，原位角膜移植被拒绝。本文还讨论了迁移的朗格汉斯细胞和角膜上皮细胞在间接途径中的作用。
Background.The immune mechanisms by which corneal allografts are rejected in normal ocular graft beds have not been identified. Both acceptors and rejectors of these types of grafts display donor-specific delayed hypersensitivity and in vitro proliferating primed T cells, yet neither develop conventional, donor-specific cytotoxic T cells. We wished to determine whether unconventional donor-specific cytotoxic T cells are generated in rejector mice that recognize donor minor alloantigens presented by recipient major histocompatibility complex (MHC) molecules.Methods.BALB/c mice received orthotopic corneal allografts from C57BL/10 donors in normal eyes. At 4 weeks (when 50% of grafts can be designated as rejected), primed cytotoxic T lymphocyte (CTL) activity in draining lymph nodes and spleen was assayed on targets selected to present donor-type minor H antigens on recipient MHC molecules. Control mice received heterotopic corneal allografts and were similarly examined.Results.Lymphoid organs of recipients that rejected orthotopic or heterotopic corneal allografts contained CTL that lysed targets expressing donor-type minor H antigens presented by recipient MHC molecules. By contrast, no CTL activity was detected from lymphoid cells of recipients that accepted orthotopic corneal allografts. Rejection of orthotopic corneal allografts placed into normal mouse eyes correlates directly with the generation of donor-specific CTL that recognize minor H antigens in the context of recipients MHC molecules.Conclusions.These results indicate the indirect pathway of alloantigen presentation is the only pathway operative in the process by which orthotopic corneal allografts are rejected. The roles of emigrant Langerhans cells and corneal lymphatics in the indirect pathway are discussed.