The role of cytotoxic T lymphocytes in corneal allograft rejection.
OBJECTIVE
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.
Hegde
S
S
Graduate Program in Immunology and. Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
Niederkorn
J Y
JY
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002460:Cell Line; D016039:Corneal Transplantation / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin