S-antigen specific T cell clones from a patient with Behçet's disease.

The isolation and characterisation of T cell clones or lines specific to retinal antigens are valuable tools to clarify the underlying mechanisms of autoimmunity to retinal antigens as a contributing factor in ocular inflammation. Patients with Behçet's disease have been reported to be sensitised to S-antigen (S-Ag). In the present study, four T cell clones established from the peripheral blood of a patient with Behçet's disease were analysed. A CD4+ T cell clone (clone 2) and a CD8+ T cell clone (clone 10) proliferated specifically to bovine S-Ag. Although these S-Ag specific T cell clones proliferated vigorously to the intact antigen, their responses to S-Ag derived synthetic peptides M and G were weak, suggesting that the sites of human T cell recognition of S-Ag may be different from those established in the experimental model. The proliferative responses of both clones (2 and 10) were inhibited by anti-HLA-DR monoclonal antibody but not by anti-HLA-class 1 monoclonal antibody. The other two clones studied, clones 6 and 30, were CD3+, CD4-, CD8-, and they did not proliferate specifically to S-Ag. Clone 6 expressed gamma delta T cell receptors (TCR) and showed non-specific cytotoxic activity toward K562 and Daudi cell lines. Clone 30 expressed alpha beta TCR, and was devoid of cytotoxic activity. Human T cell lines and clones specific to retinal antigens will provide the framework necessary to examine the events that lead to ocular inflammation.

Effects of the immunosuppressant FK506 on a penetrating keratoplasty rejection model in the rat.

PURPOSE: The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model. METHODS: Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry. RESULTS: The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas. CONCLUSIONS: These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.