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.