Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice

PURPOSE. To determine whether cytotoxic T cells of the direct alloreactive type are activated and responsible for early, acute failure of orthotopic c orneal allografts observed in eyes of C57BL/6 but not of BALB/c mice. METHODS. Corneas from BALB/c and BALB.B mice were placed orthotopically in eyes of C57BL/6 and beta -2 microglobulin knockout mice (deficient in CD8() cytotoxic T cells). Graft fates were assessed clinically, and the T lymph ocytes of recipients were assayed for the capacity to lyse target cells bea ring donor major (MHC) and/or minor histocompatibility (minor H) antigens ( direct and indirect pathways, respectively). RESULTS. Similar to BALB/c recipients, C57BL/6 mice with rejected cornea al lografts acquired donor minor H-specific T cells. Unlike BALB/c recipients, C57BL/6 mice-both rejectors and acceptors-acquired donor MHC-specific T ce lls. beta -2 Microglobulin knockout mice showed rejection of corneal allogr afts in a manner indistinguishable from C57BL/6 mice, including early, acut e rejection, yet T cells from beta -2 microglobulin knockout recipients of corneal allografts dis played no cytotoxic T cells specific for either dono r MHC or minor H alloantigens. CONCLUSIONS. Although C57BL/6 mice acquired donor MHC-specific cytotoxic T cells (direct alloreactive cells), neither these cells nor donor minor H-sp ecific cytotoxic T cells (indirect alloreactive cells) play any essential r ole in corneal allograft rejection, including the early acute failure uniqu ely observed in C57BL/6 eyes.