Factors affecting rejection of second corneal transplants in rats

Background. Second and subsequent corneal transplants in the same eye are more prone to rejection reactions and failure than first grafts. This may be a result of local changes or systemic sensitization to antigen shared by the first and second donors. Because HLA typing is not routine in corneal transplantation, a clear correlation between accelerated rejection and specific sensitization has not been established. Methods. PVG (RT1(c)), Lewis (LEW; RT1(1)) or AO (RT1(u)) strain corneas were transplanted to PVG strain rats, followed by a LEW strain cornea in the ipsilateral or contralateral eye 6 weeks later. Graft survival was evaluated by slit lamp biomicroscopy. Proliferation of recipient lymph node cells was tested against allogeneic, syngeneic and third-party stimulator cells after the second transplantation. Results. A second allograft in the ipsilateral or contralateral eye was rejected in an accelerated fashion that was not donor MHC specific. Rejection was not significantly accelerated in the ipsilateral eye compared with the contralateral eye. There was a secondary lymphocyte proliferation response to third party (AO strain) in animals previously exposed only to the LEW strain. Conclusions. Systemic sensitization to donor antigens, rather than local changes induced by first transplantation, contributed to accelerated rejection of a second graft. Accelerated rejection is not dependent on MHC compatibility between the grafts. It could be caused by shared "public" MHC determinants, by minor antigens shared by the first and second donors, or by cross-reactivity of T cells to epitopes on AO and LEW grafts. HLA mismatching of first and second donors may not prolong second graft survival.