T-cell mediated responses in a murine model of orthotopic corneal transplantation

To evaluate the role that delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte responses play in a murine model of orthotopic corneal allograft transplantation.

Corneal transplantation was performed by grafting C57BL/6 donor corneas into BALB/c corneal beds. After transplantation, the mice were observed by slit lamp biomicroscopy on a weekly basis and graded for signs of graft rejection and delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) responses to donor alloantigens assessed at selected times after grafting.

It was determined that between 40% and 65% of BALB/c mice rejected C57BL/6 corneas by 8 weeks after engraftment. Mice with opacity 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 C57BL/6 alloantigens and are primarily directed against non-major histocompatibility complex (MHC) C57BL/6 alloantigens and are primarily directed against non-major histocompatibility complex C57BL/6 alloantigens, as evidenced by the ability of B10.D2 cells to elicit DTH responses whereas C.B10-H-2b cells did not. However, although BALB/c mice engrafted with C57BL/6 tail skin demonstrated significantly greater CTL activity than naive BALB/c mice, there was no significant difference in CTL activity between BALB/c mice whose C57BL/6 corneal allografts displayed opacity scores greater than (rejected) or less than (accepted) 2.

The mechanism whereby corneal allografts in this strain combination are rejected is best associated with the ability to generate strong DTH responses and not CTL activity. This DTH response also demonstrates alloantigen specificity and appears to be primarily directed against the non-MHC component of the corneal transplant.