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 infi ltrating T-cell lines that were propagated from biopsy and nephrectomy specimens designated as IG-Bip and IG-Neph, respectively, or analogou s line designated IG-T-eff, which was generated by co-culturing pretra nsplant 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 o f 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-Nep h and IG-T-eff lines had equal mixture of CD4(+) (34%) and CD8(+) (38% ) subsets). Functionally, all three lines contained donor-specific CTL s. In the present report, we used the in vitro MLR to examine the poss ible utilization of these CTL lines as inducer cells to generate donor -specific Ts cells from recipient PBLs. Coculturing IG-PBL that was dr awn before or after transplantation and immunosuppression with irradia ted 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 inhi bited MLR response of recipient PBLs against donor or third-party stim ulators that shared with the donor the mismatched HLA antigens. Ts sup pression was more pronounced against early phase of MLR response and w as not due to a shift in MLR kinetics or nonspecific soluble suppresso r or cytotoxic products. These findings suggest that allograft infiltr ating CTLs or their in vitro generated analogous line may modulate all ograft rejection by acting as Ts inducers and that Ts induction was de pendent on the presence of the CD4 subset within the Ts-inducer cells but was not dependent on renal transplantation or immunosuppression.