EFFECT OF TOPICALLY APPLIED ANTI-CD4 MONOCLONAL-ANTIBODIES ON ORTHOTOPIC CORNEAL ALLOGRAFTS IN A RAT MODEL

Purpose. Monoclonal antibodies (mAb) have generated interest as therap eutic agents. Limited data are available on the treatment of corneal g raft rejection. The purpose of this study was to assess the use of top ically applied mAb on experimental corneal grafts. Methods, W 3/25, an Ige 1 mouse antirat mAb that recognizes a CD4+ cell subset, was used to treat Lewis recipient rats that received orthotopic corneal grafts of Wistar-Furth donors. Recipients were randomly assigned to receive t opically applied drops of liposome-incorporated anti-CD4 mAb (LIP-anti -CD4 mAb), an equivalent amount of free anti-CD4 mAb, an isotype-match ed control mAb encapsulated in liposomes (LIP-control mAb), or empty l iposomes (emp-LIP) 5 times daily for 10 days. To investigate the immun ologic effect of mAb treatment, flow cytometry of the targeted cells a nd cytotoxic activity of lymphocytes were analyzed. Results. Applicati on of LIP-anti-CD4 mAb was effective in reducing the rejection rate (P < .05) and in prolonging the mean survival time of corneal grafts tha t underwent rejection (P < .05). In contrast, no significant effect on graft outcome was observed after the application of control agents. F low cytometry analysis did not reveal systemic depletion of the target ed lymphocyte subset in any anti-CD4 mAb treated animals. Rejected gra fts elicited a cellular cytotoxic immune response in a cell-mediated l ymphocytotoxic assay independent of the treatment given. Conclusion. T he results suggest that treatment with topically applied LIP-anti-CD4 mAb prolongs graft survival in orthotopic corneal grafts in a rat mode l, The beneficial effect of LIP-anti-CD4 mAb, probably due to enhanced intraocular delivery, was achieved by using relatively low doses of m Ab.