Inverse relationship between immune interferon induction and mitogen effects on the maturation of the primary...

Staphylococcal enterotoxin A (SEA) is both a potent inducer of immune interferon (IFN-gamma) and suppressor of the murine primary in vitro plaque-forming cell (PFC) response to the thymus-dependent antigen sheep erythrocytes (SRBC). Staphylococcal enterotoxin D (SED), which is structurally related to but antigenically different from SEA, is, in contrast, a poor inducer of IFN-gamma but a potent accelerator of PFC response maturation. SED added to cultures from 0.01 to 1.0 microgram/ml induced profound enhancement of the PFC response on day 3 of culture. SEA caused no acceleration of PFC maturation and suppressed the day 5 PFC response over an equivalent dose range. At the same concentration, SED only poorly induced IFN-gamma, while SEA was a potent IFN-gamma inducer. SED induced DNA synthesis in C57Bl/6 spleen cell cultures but not athymic nude (Nu/Nu) spleen cells, suggesting that SED is a T-cell mitogen. SED was most effective in accelerating PFC maturation and increasing the magnitude of the PFC response when added to cultures at the time of SRBC addition. SED was an equally effective adjuvant for SRBC of both high and low immunogenicity. Thus, two mitogens that are structurally related have diametrically opposite effects on the primary in vitro thymus-dependent antibody response that maybe related to their relative abilities to induce IFN-gamma. These effects could be related to differential activation of T-cell subpopulations.