Mechanism of suppression of lymphocyte proliferation by Concanavalin A-activated mononuclear cells.

In this study, the mechanism by which Concanavalin A (Con A) pre-treated lymphocytes suppress mitogen-induced proliferation of responder cells was investigated. Responder-cell proliferation could only be suppressed when these cells were co-cultured with the Con A pre-treated cells but not with their supernatants, nor in chambers where the suppressor cells were separated from the responder cells by a millipore filter. Suppression could not be mediated by heat-killed Con A-activated cells or lysates from these cells. Trypsinization of the Con A-induced suppressor cells resulted in loss of suppressor activity which could be restored if the cells were allowed to recover overnight. Trypsinization of the responder cells, however, before their co-culture with the Con A pre-treated cells did not affect suppression. Addition of cytochalasin B to the co-culture resulted in reduced suppression and cycloheximide treatment of the suppressor cells abolished their activity. The results indicate that for optimal suppression to occur, cell-to-cell contact is required and viable, intact Con A-inducible suppressor cells, actively synthesizing protein are essential. Furthermore, suppression may be mediated via a membrane receptor on the suppressor cell as manipulations of normal membrane function may abolish suppression.