Regulation of human cytotoxic lymphocyte responses. I. Non-cytolytic suppression mediated by alloantigen-activated cells.

Alloantigen sensitized human lymphocytes obtained from a 2-3 day mixed lymphocyte culture (MLC) suppressed the in vitro generation of alloreactive cytotoxic lymphocytes (CTL). The inhibition of CTL responses was demonstrated in MLC after both 1 day and 14 days' allosensitization. The suppressor cells were nylon wool non-adherent, lacked Fc receptors and adhered to histamine columns. The MLC-activated suppressor cell population had an associated very low and transient cytotoxic response directed against the allogeneic sensitizing cell. Several procedures were used to dissociate this activity from suppressor cell function: (1) donors were preselected which showed minimal cross-killing between allogeneic stimulating cells, (2) suppressor cultures were added to the test cultures prior to the development of maximal CTL activity, (3) suppressor cultures were irradiated preventing cell proliferation associated with differentiating CTL. Lastly, by increasing stimulating antigen concentration suppressor cell activity was increased rather than being competitively diminished, which would be predicted if suppression was occurring through a cytolytic or inactivation of stimulating antigen. It was therefore concluded that alloantigen stimulation in MLC activates a non-cytolytic regulatory cell population which is capable of inhibiting CTL responses to third-party allogeneic lymphocytes.