T-cell-mediated immune responses in alloepithelial rejection after murine keratoepithelioplasty

PURPOSE. TO evaluate the role of delayed-type hypersensitivity (DTH) and cy totoxic T-lymphocyte (CTL) responses on alloepithelial rejection in a murin e keratuepithelioplasty model. METHODS. C3H/He mouse corneal lenticules were grafted around the limbus in BALB/c mice, and alloepithelial rejection was assessed by microscopic evalu ation. The relation between rejection scores and DTH or CTL responses to do nor antigens was assessed by Spearman correlation analysis. Suppression of DTH responses by induction of anterior chamber-associated immune deviation (ACAID) was used to evaluate-the contribution of DTH responses to allograft rejection. CTL responses were evaluated by in vitro and in vivo depletion of CD4(+) or CD8(+) cells. RESULTS. DTH responses, which developed 2 weeks postoperatively, correlated significantly With rejection scores (correlation coefficient r = 0.55). AC AID induction by anterior chamber inoculation of C3H/He splenocytes signifi cantly suppressed allospecific DTH responses and alloepithelial rejection. While allospecific Cn responses also developed 2 weeks postoperatively and increased by 4 weeks, CTL responses did not exhibit positive correlation wi th rejection scores (r = -0.36, P = 0.076). The CTL responses were mediated exclusively by CD8(+) cells. Although in vivo depletion of CD8(+) cells ab olished the induction of CTL responses, it did not prevent allograft reject ion. Immunohistochemistry showed infiltration of CD4(+) and CD8(+) cells in to the alloepithelium. Positive staining for interferon gamma but not inter leukin 4 further implicated the participation of a DTH response. CONCLUSIONS. Allograft rejection after keratoepithelioplastry appears to be mediated primarily by DTH responses, with CTL responses playing only a min or role perhaps in modifying the development of rejection.