Specific suppression of mixed lymphocyte reactions by alloactivated cells is correlated with cytotoxicity

Abstract

Mixed lymphocyte reaction (MLR)-activated lymphoblasts can suppress both proliferation and the induction of cell-mediated lysis (CML) when added to a subsequent MLR. Antigen specificity and the mechanism of MLR-induced suppression was investigated, with special emphasis on the exclusion of cell-mediated stimulator cell lysis as the cause of suppression. We studied the suppressive properties of nine MLR-activated cultures, selected because of their specific suppressive properties. Suppression of a given MLR was obtained when the stimulator cell carried at least one of the mismatched HLA antigens of the original stimulator. The mismatched antigen which activated suppression was an HLA class I antigen in 3 out of 9 cases, an HLA class II antigen in another 3 cases. In the remaining 3 cases suppression was observed when either an HLA class I or an HLA class II antigen was shared between the original stimulator and stimulator cell of the MLR. When analyzed on the same panel, a positive linear correlation between suppression of an MLR and CML activity against the stimulator cell was found. We also observed that both the original MLR (A ∗B) and the reverse MLR (B ∗A) could be suppressed by these anti-A suppressor cells. These results are compatible with the hypothesis that in the protocol studied suppression is mediated by lysis of the stimulator cells.