T-CELL MEDIATED RESPONSES IN A MURINE MODEL OF ORTHOTOPIC CORNEAL TRANSPLANTATION

Purpose. To evaluate the role that delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte responses play in a murine model of orthot opic corneal allograft transplantation. Methods. Corneal transplantati on was performed by grafting C57BL/6 donor corneas into BALB/c corneal beds. After transplantation, the mice were observed by slit lamp biom icroscopy on a weekly basis and graded for signs of graft rejection an d delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) responses to donor alloantigens assessed at selected times after graf ting. Results. It was determined that between 40% and 65% of BALB/c mi ce rejected C57BL/6 corneas by 8 weeks after engraftment. Mice with op acity scores >2 demonstrated significantly greater DTH responses than did mice with opacity scores <2 at 2, 3, and 4 weeks after engraftment . After 4 weeks, the DTH responses for all groups were essentially the same as for naive BALB/c mice. The DTH responses were specific for C5 7BL/6 alloantigens and are primarily directed against non-major histoc ompatibility complex (MHC) C57BL/6 alloantigens and are primarily dire cted against non-major histocompatibility complex C57BL/6 alloantigens , as evidenced by the ability of B10.D2 cells to elicit DTH responses whereas CB10-H-2(b) cells did not However, although BALB/c mice engraf ted with C57BL/6 tail skin demonstrated significantly greater CTL acti vity than naive BALB/c mice, there was no significant difference in CT L activity between BALB/c mice whose C57BL/6 corneal allografts displa yed opacity scores greater than (rejected) or less than (accepted) 2. Conclusions. The mechanism whereby corneal allografts in this strain c ombination are rejected is best associated with the ability to generat e strong DTH responses and not CTL activity. This DTH response also de monstrates alloantigen specificity and appears to be primarily directe d against the non-MHC component of the corneal transplant.