Corneal allografts induce cytotoxic T cell but not delayed hypersensitivity responses in mice

In order to study the cellular immune responses induced by corneal allografts transplanted to a nonimmunologically privileged site, we have used a previously described murine heterotopic corneal allograft model. BALB/c (H-2(d)) corneal allografts transplanted to a vascular graft bed on the thorax of C57BL/6 (H-2(b)) recipients were rapidly rejected within 14 days, while corneal syngrafts survived indefinitely (>28 days). Analysis of both primary and secondary cytotoxic T lymphocyte (CTL) responses 7, 10, 14, and 21 days after heterotopic transplantation revealed antigen-specific CTL reactivity at all time points tested (P<0.01). By contrast, delayed-type hypersensitivity (DTH) responses to corneal alloantigens (footpad swelling assay) were negative (P>0.05) in 83% of the animals tested. The absence of DTH responsiveness to corneal allografts was not a result of the small graft size or antigenic load. Either two or six circular skin allografts (3-mm diam) of BALB/c origin induced both strong CTL and DTH responses (P<0.001) in C57BL/6 recipients, while two or six corneal allografts (2-mm diam) induced strong CTL responses, but DTH responses again failed to develop (P>0.05) in over 75% of the animals tested. The ability of corneal alloantigens to elicit CTL responses but not DTH reactivity when grafted to a heterotopic site provides a basis for understanding the immune privilege enjoyed by this tissue.