Cytotoxic T-cell role in renal allograft rejection and regulation. Renal allograft infiltrating cytotoxic T-cell line with suppressor-inducer function.

We previously investigated the characteristics of renal allograft infiltrating T-cell lines that were propagated from biopsy and nephrectomy specimens designated as IG-Bip and IG-Neph, respectively, or analogous line designated IG-T-eff, which was generated by co-culturing pretransplant recipient blood with irradiated donor splenocytes (manuscript submitted). The recipient (IG) had no previous sensitization to donor mismatched HLA antigens (A2 and DR1). Phenotypically, all lines were of recipient origin and were CD3+, TCR alpha beta +, DR+. However IG-Bip line was low in CD4 (19%) and high in CD8 (50%), whereas IG-Neph and IG-T-eff lines had equal mixture of CD4+ (34%) and CD8+ (38%) subsets). Functionally, all three lines contained donor-specific CTLs. In the present report, we used the in vitro MLR to examine the possible utilization of these CTL lines as inducer cells to generate donor-specific Ts cells from recipient PBLs. Coculturing IG-PBL that was drawn before or after transplantation and immunosuppression with irradiated IG-T-eff or IG-Neph but not IG-Bip CTL lines, generated Ts cells. Ts cells were of recipient origin and were CD3+, CD8+, leu 11b+, CD28-, all characteristic of Ts-effector phenotype. Ts cells inhibited MLR response of recipient PBLs against donor or third-party stimulators that shared with the donor the mismatched HLA antigens. Ts suppression was more pronounced against early phase of MLR response and was not due to a shift in MLR kinetics or nonspecific soluble suppressor or cytotoxic products. These findings suggest that allograft infiltrating CTLs or their in vitro generated analogous line may modulate allograft rejection by acting as Ts inducers and that Ts induction was dependent on the presence of the CD4 subset within the Ts-inducer cells but was not dependent on renal transplantation or immunosuppression.