The Role of Cytotoxic T Lymphocytes in Corneal Allograft Rejection

Immunologic rejection constitutes a major barrier to the success of allogeneic corneal transplants, but the specific mediators and mechanisms of graft rejection are poorly understood. Several studies have implicated cytotoxic T-lymphocyte (CTL) responses, typically associated with CD8(+) T cells, in promoting corneal graft rejection. This study sought to test the hypothesis that CTLs are essential in promoting corneal graft rejection. BALB/c donor corneas were grafted orthotopically onto C57BL/6, perforin knockout, or CD8(+) T-cell knockout mice. The tempo and incidence of graft rejection were observed for each group. In separate experiments, donor-specific CTL and delayed-type hypersensitivity (DTH) responses were tested at the time of graft rejection by a standard chromium release assay and an ear swelling assay, respectively. Perforin knockout and CD8(+) T-cell knockout mice were as effective as wild-type C57BL/6 control mice in rejecting BALB/c donor corneas. Furthermore, animals in all three groups were found to develop robust donor-specific DTH, not CTL, responses at the time of graft rejection. Histopathologically, the rejected corneas from all three groups contained a predominantly mononuclear cellular infiltrate. This study rejects the hypothesis that CD8(+) CTLs are essential in promoting corneal graft rejection and instead further implicates donor-specific DTH reactions as the relevant immune response during graft failure.