Sano Y, Ksander B R, Streilein J W
Schepens Eye Research Institute, Boston, MA 02114, USA.
Transpl Immunol. 1996 Mar;4(1):53-6. doi: 10.1016/s0966-3274(96)80035-9.
Irrespective of HLA matching, a far higher proportion of human corneal allografts placed orthotopically in avascular corneal graft beds are accepted indefinitely, compared to other types of solid tissue allografts. However, many more corneal grafts are rejected if they are transplanted onto neovascularized recipient eyes. Using a murine model of orthotopic corneal transplantation in which grafts were placed in normal eyes, we have reported previously that grafts bearing minor H antigens alone are more likely to be rejected (approximately 50%) than are grafts displaying only MHC alloantigens (< 20%). Moreover, recipients of MHC plus minor H incompatible corneal grafts developed delayed hypersensitivity (DH) directed solely at minor H antigens. These studies have now been extended to include corneal grafts placed in neovascularized recipient eyes. Neovascularization was induced by placing sutures in the central cornea of one eye of BALB/c mice. Two weeks later corneas from C57BL/10 donors were grafted into these eyes. Rejection reactions were first apparent within 7 days and all grafts were destroyed by 14 days. Donor-specific DH responses were examined by injecting irradiated donor antigen-bearing spleen cells into the ear pinna. To distinguish DH directed at MHC versus minor antigens, some graft recipients were ear-challenged with BALB.B cells (donor MHC only), while other received B10.D2 cells (donor minor H only). Intense ear-swelling responses were evoked by B10.D2 cells, but not by BALB.B cells. These findings indicate that, for orthotopic corneal allografts, minor H antigens offer a more formidable barrier to graft acceptance than do MHC-encoded antigens. We speculate that this unexpected outcome may reflect a reduced level of MHC expression on corneal tissue. Moreover since the cornea lacks bone marrow derived dendritic cells, allorecognition by recipient T cells must occur via the indirect pathway, and in this situation minor H antigens may compete favorably with MHC antigens for processing and presentation by recipient antigen-presenting cells.
与其他类型的实体组织同种异体移植相比，无论 HLA 是否匹配，原位植入无血管角膜移植床的人类角膜同种异体移植被长期接受的比例要高得多。然而，如果将更多的角膜移植到新生血管化的受体眼中，它们就会被排斥。利用原位角膜移植的小鼠模型，将移植物植入正常眼睛，我们之前报道过，仅携带次要组织相容性抗原（minor H antigens）的移植物比仅显示 MHC 同种异体抗原的移植物更容易被排斥（约 50% 对 < 20%）。此外，MHC 加次要组织相容性抗原不相容的角膜移植受体产生了仅针对次要组织相容性抗原的迟发型超敏反应（DH）。这些研究现已扩展到包括植入新生血管化受体眼中的角膜移植。通过在 BALB/c 小鼠一只眼睛的中央角膜放置缝线来诱导新生血管形成。两周后，将来自 C57BL/10 供体的角膜移植到这些眼睛中。排斥反应在 7 天内首次明显出现，并在 14 天内所有移植物均被破坏。通过将经辐照的携带供体抗原的脾细胞注射到耳廓来检测供体特异性 DH 反应。为了区分针对 MHC 与次要抗原的 DH，一些移植物受体用 BALB.B 细胞（仅供体 MHC）进行耳部攻击，而其他受体接受 B10.D2 细胞（仅供体次要组织相容性抗原）。B10.D2 细胞引起强烈的耳部肿胀反应，但 BALB.B 细胞未引起。这些发现表明，对于原位角膜同种异体移植，次要组织相容性抗原比 MHC 编码的抗原对移植物接受提供了更强大的障碍。我们推测这种意外结果可能反映了角膜组织上 MHC 表达水平的降低。此外，由于角膜缺乏骨髓来源的树突状细胞，受体 T 细胞的同种异体识别必须通过间接途径发生，在这种情况下，次要组织相容性抗原可能在受体抗原呈递细胞对其进行加工和呈递方面比 MHC 抗原更具优势。
