Regulation of human cytotoxic lymphocyte responses. II. Suppression by a soluble factor produced by primed lymphocytes.

A soluble supernatant factor is elaborated from in vitro primed human allogeneic lymphocytes which suppresses the development of alloreactive cytotoxic lymphocytes (CTL). In contrast, supernatants obtained from primary mixed lymphocyte cultures (MLC) and primed autologous cultures were unable to suppress CTL activation, indicating that antigen restimulation was required to elicit the factor. The suppressor factor (SF) functioned in a dose-dependent manner. When the SF was added 24 or 48 hr after MLC initiation it was ineffective. However, adding the SF at culture initiation significantly reduced CTL activity, suggesting that suppression occurs either during antigen recognition or early in the CTL differentiation pathway. The SF did not function by altering the kinetics of the CTL response. Preincubation experiments showed that the SF operates by partially inactivating both MLC responder and stimulator cell populations.