The role of cytotoxic T lymphocytes in corneal allograft rejection

PURPOSE. Immunologic rejection constitutes a major barrier to the success o f 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. METHODS. BALB/c donor corneas were grafted orthotopically onto C57BL/6, per forin knockout, or CD8(+) T-cell knockout mice. The tempo and incidence of graft rejection were observed for each group. In separate experiments, dono r-specific CTL and delayed-type hypersensitivity (DTH) responses were teste d at the time of graft rejection by a standard chromium release assay and a n ear swelling assay, respectively. RESULTS. Perforin knockout and CD8(+) T-cell knockout mice were as effectiv e as wild-type C57BL/6 control mice in rejecting BALB/c donor corneas. Furt hermore, animals in all three groups were found to develop robust donor-spe cific DTH, not CTL, responses at the time of graft rejection. Histopatholog ically, the rejected corneas from all three groups contained a predominantl y mononuclear cellular infiltrate. CONCLUSIONS. This study rejects the hypothesis that CD8(+) CTLs are essenti al in promoting corneal graft rejection and instead further implicates dono r-specific DTH reactions as the relevant immune response during graft failu re.