Ksander B R, Sano Y, Streilein J W
Schepens Eye Research Institute, Boston, MA 02114, USA.
Transpl Immunol. 1996 Mar;4(1):49-52. doi: 10.1016/s0966-3274(96)80034-7.
Clinical ophthalmologists are highly successful in grafting allogeneic corneas onto healthy eye graft beds--only a small percentage are rejected. By contrast, a high percentage of allografts are rejected when grafted into vascularized or '"high-risk' recipient eyes. The following experiments test the hypothesis that donor-specific cytotoxic T cells mediate graft rejection in high-risk, but not normal, eyes. MHC plus minor histoincompatible C57BL/6 corneas were grafted orthotopically onto BALB/c mice. Healthy recipient eyes were trephined and served as normal graft beds; corneal vascularization was induced by penetrating sutures and these eyes served as 'high-risk' graft beds. Cytotoxic T cells were assayed at 2 and 8 weeks postgrafting using either draining cervical lymph nodes or spleen cells restimulated for 3 days with irradiated allogeneic splenic stimulator cells. As a positive control, donor-specific cytotoxic T cells were induced in mice immunized by subcutaneous injection of allogeneic spleen cells. A low percentage (only 50%) of corneal allografts were rejected when placed orthotopically onto normal healthy eyes. Donor-specific cytotoxic cells were not detected in the draining lymph nodes or spleens of mice that either accepted, or rejected their corneal graft. The failure to detect cytotoxic T cells was not due to anergy or the deletion of allospecific precursors of cytotoxic T cells. By contrast, 97% of corneal allografts were rejected from high-risk recipient eyes (no immune privilege). Donor-specific cytotoxic T cells were routinely detected in the draining lymph nodes of these mice and their appearance coincided with graft rejection. We conclude that allografts placed onto normal healthy eyes fail to induce donor-specific cytotoxic T cells. In the absence of specific cytotoxic T cells, other alloimmune effectors are less successful at mediating rejection. By contrast, allografts placed onto high-risk eyes induce donor-specific cytotoxic T cells, and all grafts are universally rejected. These results imply that immune privilege can protect corneal allografts from most effector mechanisms, except cytotoxic T cells.
临床眼科医生在将同种异体角膜移植到健康眼植床方面非常成功，只有一小部分会被排斥。相比之下，当同种异体移植物移植到血管化或“高风险”受体眼中时，很大比例会被排斥。以下实验检验了这样一个假设：供体特异性细胞毒性T细胞在高风险而非正常眼中介导移植物排斥。将主要组织相容性复合体（MHC）加上次要组织不相容的C57BL/6角膜原位移植到BALB/c小鼠上。对健康受体眼进行环钻并作为正常植床；通过穿透性缝线诱导角膜血管化，这些眼作为“高风险”植床。在移植后2周和8周，使用引流颈淋巴结或用经辐照的同种异体脾刺激细胞再刺激3天的脾细胞来检测细胞毒性T细胞。作为阳性对照，通过皮下注射同种异体脾细胞免疫小鼠来诱导供体特异性细胞毒性T细胞。当原位移植到正常健康眼上时，只有低比例（仅50%）的角膜同种异体移植物被排斥。在接受或排斥角膜移植的小鼠的引流淋巴结或脾脏中未检测到供体特异性细胞毒性细胞。未能检测到细胞毒性T细胞并非由于无反应性或细胞毒性T细胞的同种特异性前体的缺失。相比之下，97%的角膜同种异体移植物从高风险受体眼中被排斥（无免疫赦免）。在这些小鼠的引流淋巴结中常规检测到供体特异性细胞毒性T细胞，并且它们的出现与移植物排斥同时发生。我们得出结论，移植到正常健康眼上的同种异体移植物未能诱导供体特异性细胞毒性T细胞。在没有特异性细胞毒性T细胞的情况下，其他同种免疫效应器在介导排斥方面不太成功。相比之下，移植到高风险眼上的同种异体移植物诱导供体特异性细胞毒性T细胞，并且所有移植物都被普遍排斥。这些结果表明，免疫赦免可以保护角膜同种异体移植物免受大多数效应机制的影响，细胞毒性T细胞除外。
