Matoba A Y, Peeler J S, Niederkorn J Y
Invest Ophthalmol Vis Sci. 1986 Aug;27(8):1244-54.
Using a previously described murine heterotopic corneal allograft model, we examined the roles of delayed-type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL) in corneal allograft rejection. We have previously shown that normal C57BL/6 mice consistently reject heterotopic corneal allografts within 14 days of grafting. These hosts develop antigen-specific CTL responses but no evidence of DTH reactivity. The absence of DTH suggested that this T cell subset was unnecessary for corneal allograft rejection. The present studies using T cell-deficient mice selectively reconstituted with specific T cell subsets confirmed this suspicion. T cell-deficient (i.e., adult thymectomized, lethally irradiated, bone marrow-reconstituted = ATXBM) C57BL/6 mice were selectively reconstituted with the following categories of syngeneic lymph node cells (LNC): BALB/c skin-immune LNC treated with anti-Lyt 1 antibody + complement; BALB/c skin- or cornea-immune LNC treated with anti-Lyt 2 antibody + complement; or BALB/c cornea- or skin-immune LNC not treated with antibody. ATXBM mice reconstituted with syngeneic Lyt 1-depleted, BALB/c skin-immunized LNC failed to develop DTH, yet rapidly rejected BALB/c corneal allografts. Similarly, ATXBM mice reconstituted with Lyt 1-depleted cornea-immune LNC did not demonstrate DTH responses but were able to reject 100% of the corneal allografts in an accelerated fashion. By contrast, corneal allograft rejection was significantly delayed in ATXBM mice reconstituted with cornea-immune LNC partially depleted of Lyt 2+ T cells. Collectively, the results indicate that: heterotopic corneal allografts can be rejected in the absence of DTH; heterotopic corneal allografts fail to induce allospecific DTH; and partial depletion of Lyt 2+ CTL leads to a prolongation of heterotopic corneal allograft survival. Thus, the primary T cell-dependent immune effector elements responsible for heterotopic corneal allograft rejection appears to reside in the cytolytic T lymphocyte population.
利用先前描述的小鼠异位角膜移植模型，我们研究了迟发型超敏反应（DTH）和细胞毒性T淋巴细胞（CTL）在角膜移植排斥反应中的作用。我们先前已表明，正常的C57BL/6小鼠在移植后14天内始终会排斥异位角膜移植。这些宿主会产生抗原特异性CTL反应，但没有DTH反应性的证据。缺乏DTH表明该T细胞亚群对于角膜移植排斥并非必需。使用用特定T细胞亚群选择性重建的T细胞缺陷小鼠的本研究证实了这一怀疑。用以下几类同基因淋巴结细胞（LNC）选择性重建T细胞缺陷（即成年胸腺切除、致死性照射、骨髓重建=ATXBM）的C57BL/6小鼠：用抗Lyt 1抗体+补体处理的BALB/c皮肤免疫LNC；用抗Lyt 2抗体+补体处理的BALB/c皮肤或角膜免疫LNC；或未用抗体处理的BALB/c角膜或皮肤免疫LNC。用同基因Lyt 1缺失、BALB/c皮肤免疫的LNC重建的ATXBM小鼠未能产生DTH，但迅速排斥了BALB/c角膜移植。同样，用Lyt 1缺失的角膜免疫LNC重建的ATXBM小鼠未表现出DTH反应，但能够以加速方式排斥100%的角膜移植。相比之下，在用部分耗尽Lyt 2 + T细胞的角膜免疫LNC重建的ATXBM小鼠中，角膜移植排斥明显延迟。总体而言，结果表明：在没有DTH的情况下异位角膜移植可以被排斥；异位角膜移植不能诱导同种异体特异性DTH；Lyt 2 + CTL的部分耗尽导致异位角膜移植存活期延长。因此，负责异位角膜移植排斥的主要T细胞依赖性免疫效应元件似乎存在于细胞溶解T淋巴细胞群体中。
