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

• Published in: Transplantation Vol. 69; no. 4; p. 483
• Main Authors: Haskova, Z, Usiu, N, Pepose, J S, Ferguson, T A, Stuart, P M
• Format: Journal Article
• Language: English
• Published: United States 27.02.2000
• Subjects: Animals; CD4-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - physiology; Corneal Transplantation - immunology; Corneal Transplantation - pathology; Female; Graft Rejection - pathology; Hypersensitivity, Delayed - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Skin Transplantation - immunology; Skin Transplantation - pathology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0041-1337
• DOI: 10.1097/00007890-200002270-00004

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. 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. 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. 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.