Effect of LFA-1 and ICAM-1 antibody treatment on murine corneal allograft survival.

PURPOSE To examine the effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on orthotopic corneal graft survival in a mouse model. METHODS Anti-LFA-1 and anti-ICAM-1 antibodies were administered intraperitoneally before and shortly after orthotopic corneal transplantation. Grafts were observed by biomicroscopy, and survival times were determined. Cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses to donor alloantigens were assessed at selected times after grafting. RESULTS Administration of anti-LFA-1 antibody reduced the incidence of graft rejection from 90% in untreated donors to 47% in anti-LFA-1 treated mice. By contrast, treatment with anti-ICAM-1 antibody alone did not reduce the incidence of rejection, although it prolonged graft survival time. Both CTL and DTH responses to donor alloantigens were severely depressed in hosts treated with either anti-LFA-1 or anti-ICAM-1 antibody. However, neither anti-ICAM-1 nor anti-LFA-1 antibody treatment prevented the rejection of orthotopic corneal grafts in previously immunized mice. CONCLUSIONS Anti-ICAM-1 antibody does not promote graft survival even though it impairs CTL and DTH responses to donor alloantigens. By contrast, anti-LFA-1 antibody can significantly reduce the incidence of orthotopic corneal graft rejection and prevent the induction of normal allospecific CTL and DTH responses. Although anti-LFA-1 antibody is effective if given prophylactically, it is ineffective at preventing corneal graft rejection in previously immunized hosts.