The effect of α/β t-cell receptor directed therapy in corneal allotransplantation

Purpose. The mechanisms of immunological responses to corneal allografts leading to inflammation, neovascularization and loss of vision remain to be defined. To determine the extent of α/β T-cell mediated immunity in corneal allograft rejection, we used a mouse anti rat monoclonal antibody (mAb R73), directed against the α/β T cell receptor, which is expressed on more than 95% of peripheral T cells, in a high responder rat to rat penetrating keratoplasty model. Methods. 3. 5 mm full thickness corneal grafts were transplanted orthotopically from male ACT to completely MHC disparate male LEWIS rats. Animals were divided into 2 experimental groups. Group (A) represented the low risk situation and received a corneal graft only (n=12). Group (B) represented the high risk situation and received a donor specific skin graft at day -7 (n=8). Experimental animals were pretreated with 0. 5 mg/kg R73 i. v. daily, starting at day -7. No antibody was given after corneal transplantation, control animals received saline only. Immunological rejection was defined as complete opacity of the donor cornea. Results. (A) o/ TCR directed therapy in naive recipients prolonged corneal graft survival to 26. 3 ± 7. Id compared to 13. 3 ±1. 9d in untreated controls and induced indefinite graft survival in 30% of cases. FACS analysis revealed a partial transient depletion of CD5+ cells; T cell profiles were normal by the time of transplantation. (B) Skin presensitization produced accelerated rejection within 7 days which could be slightly prolonged to 10. 8 ± 1. 3d by pretreatment with the mAb R73. Conclusions, ct/ TCR targeted therapy in the rat prolongs corneal allograft survival by induction of a state of hyporesponsiveness when used before the alloantigenic exposure. The effect is markedly reduced in presensitized recipients and weaker compared to that reported for vascularized organ transplantation models. Our results indicate that α/β T-cell mediated reactions account for only a portion of the immune response leading to corneal allograft rejection.