Neutralization of T-replacing factor by T8-positive lymphocytes: an important suppressor mechanism operating in the regulation of polyclonal B-cell activation.

Pokeweed mitogen (PWM)-induced B-cell activation was entirely abrogated by pre-treating peripheral mononuclear cells (PBM) with T4 (anti-T-helper-inducer subset) or T11 (anti-sheep erythrocyte receptor, ie. anti-pan-T-cell) monoclonal antibody plus complement. Immunoglobulin secretion was restored in T11- but not T4- cultures by adding the culture supernatant from PWM-stimulated PBM (T-replacing factor, TRF). Since T8+ (T-suppressor-cytotoxic subset) cells were present in high concentrations in T4- but absent from T11- cultures, it appeared that these cells could inhibit B-cell activation by PWM plus TRF and that suppression could occur in the absence of T4+ cells. Incubation of TRF with purified, unstimulated T8+ cells prior to addition to T11- cultures abrogated subsequent PWM-induced B-cell activation, whereas T8- PBM had no effect on TRF. T8+ cells did not secrete suppressor factors during incubation with TRF. Absorption of one or more of the factors required for B-cell growth and differentiation by T8+ cells appears to be an important suppressor mechanism operating in the PWM system.