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. Conclusion. 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.