Role of CD4(+) T cells in immunobiology of orthotopic corneal transplants in mice

PURPOSE. TO determine, with the use of mice genetically deficient in expres sion of CD4 or CD8 molecules, which T cells are responsible for rejection o f orthotopic corneal allografts in mice. METHODS. Corneas were prepared from major histocompatibility complex (MHC)- only incompatible, minor histocompatibility (H)- only incompatible, and MH C-plus-minor H incompatible donors and grafted orthotopically to eyes of CD 4 knockout (KO), CD8KO, and wild-type control mice. Graft survival patterns were assessed clinically and compared. Mice that retained healthy corneal allografts beyond 8 weeks were evaluated for evidence of donor-specific tol erance and anterior-chamber-associated immune deviation (ACAID) using local adoptive transfer reactions and challenge with orthotopic skin allografts. RESULTS. Corneas grafted to CD8KO mice were rejected with an incidence and tempo indistinguishable from that in wild-type control animals. By contrast , MHC-only, and minor-H-only incompatible corneal grafts survived indefinit ely in eyes of CD4KO mice, approximately 50% of corneal grafts that confron ted CD4KO recipients with both MHC anti minor H alloantigens experienced de layed rejection, whereas similar grafts in wild-type recipients were reject ed acutely. CD4KO mice with long-accepted grafts displayed neither donor-sp ecific ACAID nor allograft tolerance. CONCLUSIONS. CD8(+) T cells play little or no role in acute rejection of or thotopic corneal allografts. Instead, acute rejection is mediated almost ex clusively by CD4(+) T cells. Moreover, when corneal allografts survive for 8 weeks without acute rejection, CD4+ T cells promote donor-specific ACAID thereby insuring long-term graft acceptance.