Analysis of primed donor-specific T cells in recipient mice bearing orthotopic corneal allografts

Background. Orthotopic corneal allografts placed in normal eyes of mice are often not rejected, whereas grafts placed in high-risk (neovascularized) e yes are routinely destroyed. Because rejection of solid tissue allografts i s usually mediated by donor-specific T cells, we wished to determine the ex tent to which donor-specific T cells become primed in mice bearing orthotop ic corneal allografts in normal and "high-risk" eyes. Methods and Results. Our data indicate corneal allografts placed in neovasc ularized eyes were rejected within 2 weeks, and lymph nodes draining these grafts contained primed donor-specific T cells that proliferated in vitro a nd displayed cytotoxic activity. By contrast, only 50% of corneal allograft s placed in normal eyes experienced rejection. Lymphoid cells from all of t hese mice displayed donor-specific proliferative activity, irrespective of whether the graft was accepted or rejected. At no time were donor-specific cytotoxic T cells detected. Failure to detect primed cytotoxic T cells was not the result of anergy or deletion of unprimed donor-specific precursors of CTL. Conclusions. We conclude that primed donor-specific proliferative and cytot oxic T cells directed at MHC alloantigens correlate well with rejection of orthotopic corneal allografts in neovascularized highrisk eyes. However, re jection of cornea allografts in normal eyes does not correlate well with pr oliferative T cells, nor are donor MMC-specific cytotoxic T cells detected. The possibility is discussed that graft rejection in normal eyes is not me diated by T cells that recognize MHC alloantigens via the direct pathway, b ut via T cells that recognize donor alloantigens presented by recipient MHC molecules (indirect pathway).