CD4+ T-cell-independent rejection of corneal allografts.
BACKGROUND
Several studies suggest that a significant number of corneal allografts undergo rejection in the absence of CD4 T cells. This study examined the role of CD4 T cell-independent mechanisms of corneal allograft rejection.


METHODS
BALB/c corneal allografts were transplanted to C57BL/6 beige nude mice that received either CD8 or CD8 T cells from C57BL/6 CD4 knockout (KO) mice that had rejected BALB/c corneal allografts. Immune effector functions of CD8 or CD8 T cells from C57BL/6 CD4 KO mice were assessed using delayed-type hypersensitivity assays and Annexin V apoptosis assays respectively. RESULTS.: Both CD8 and CD8 T cells from CD4 KO corneal allograft rejector mice mediated corneal allograft rejection following adoptive transfer to nude mice. CD8 T cells, but not CD8 T cells, from CD4 KO mice adoptively transferred donor-specific DTH and induced apoptosis of BALB/c corneal endothelial cells in vitro. Apoptosis of BALB/c corneal endothelial cells was mediated by double negative (DN) T cells, as treatment of CD8 cells from CD4 KO mice with anti-Thy 1.2 plus complement abolished their effector function.


CONCLUSIONS
The results support the proposition that CD4 T cell-independent rejection of corneal allografts can be mediated by either CD8 or CD8 T cells. The CD8 T cells represent a unique DN T cell population that might mediate rejection by either direct cytolysis or by inducing apoptosis of the donor corneal endothelium.
Niederkorn
Jerry Y
JY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Stevens
Christina
C
Mellon
Jessamee
J
Mayhew
Elizabeth
E
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D016039:Corneal Transplantation / Q000276:immunology*; D019573:Epithelium, Corneal / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous