Human suppressor cells: evidence of functionally distinct subsets

Human suppressor cells (SC) differing in both kinetic characteristics and degree of specificity were induced in vitro either by Concanavalin A (CON A) (10 μg/ml) or by repeated stimulation with allogeneic cells. CON A SC caused a characteristic early peak in blastogenesis (Day 2) when cocultured with fresh autologous cells in the presence of either CON A or allogeneic cells, although CON A SC alone did not respond to these stimuli. This early augmented response fell rapidly to values 50-90% below positive controls by the usual optimal day for the particular stimulus. Treatment with 5-bromodeoxyuridine and light during rapid proliferation ablated the early responses but increased the later responses (i.e., reduced the suppression). The cells mediating both the early rise and late suppression were found to belong to a subset of T cells that lost their ability to form SRBC rosettes (theophylline sensitive) in the presence of the phosphodiesterase inhibitor, theophylline, and were inactivated by mitomycin C. In contrast, SC induced by repeated allogeneic stimulation were suppressive in MLC but not CON A cultures, did not initiate early blastogenesis in the presence of naive cells and were partially mitomycin resistant. The mitomycin resistant SC induced by allogeneic stimulation are found in the theophylline resistant T-cell subset. These data are consistent with a model of human SC differentiation in which at least two subsets may be present: (1) a mitomycin sensitive, nonspecific cell that participates in an obligatory early autologous recognition event (induction?) and (2) a later occurring, more mitomycin resistant effector cell that appears to acquired specfficity for the response that it affects.