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1 From the Graduate Program in Immunology and 2 Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas.
PURPOSE. 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.
METHODS. 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.
RESULTS. 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.
CONCLUSIONS. 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.
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