CD4⁺ T cells are critical, for corneal, but not skin, allograft rejection

Background. The relative contribution of CD4⁺ or CD8⁺ T cells in allograft rejection remains to be fully characterized. Some reports indicate that there is an absolute requirement for CD4⁺ T cells in allogeneic rejection, whereas others report that CD4-depleted mice are capable of rejecting certain types of allografts. Methods. We compared the ability of CD4^- knockout (KO), CD8^- KO, and normal CD4⁺/CD8⁺ mice to reject allogeneic corneal or skin grafts. We also examined delayed-type hypersensitivity and CTL responses to donor alloantigens. Results. Engraftment of C57BL/6 corneas to C.B6(n5-7) CD4^-KO mice resulted in significantly higher rates of acceptance (>85%) than either C.B6-(n5-7) CD8^- KO (30%) or normal BALB/c mice (40%). Likewise, mean survival times for B6 skin grafts placed on C.B6-(n5-7) CD4^- KO mice (29,2 ± 3.5 days) were significantly increased over those of normal BALB/c mice (13.2 ± 1 days), although most CD4^- KO mice (70%) eventually reject their grafts. C.B6-(n5-7) CD4^- KO mice that reject allogeneic grafts fail to develop a delayed-type hypersensitivity response, but they did demonstrate significantly greater cytotoxic T lymphocyte precursor (CTLp) frequencies than did CD4^- KO mice that accepted such grafts or that were not grafted. Conclusions. This study indicates that mice lacking CD4⁺ T cells have a significantly impaired ability to reject corneal allografts, but are able, in most cases, to reject allogeneic skin grafts. Thus, in the absence of CD4⁺ T cells, the likely mechanism for rejection appears to involve the generation of CD8⁺ CTLs.