Two different pathways of interferon mediated suppression of antibody secretion.

Interferon suppresses a variety of in vitro immune responses by a mechanism which has not been well defined. Both direct suppression and activation of suppressor T cells have been suggested as possible mechanisms of interferon action. In an attempt to examine this question interferon-alpha (IFN alpha)-mediated suppression of a plaque forming cell response to a T cell independent antigen by spleen cells or by B cells was examined. Somewhat greater quantities of IFN alpha were required to suppress plaque forming cell responses by B cells than by spleen cells to the antigen fluoresceinated-Brucella abortus (FITC-BA). However, suppression of spleen cell responses could be blocked by addition of either 2-mercaptoethanol, levamisole or monoclonal antibodies against the lymphokine, soluble immune response suppressor (SIRS), whereas suppression of B cell responses by interferon-alpha was unaffected by these agents. Each of these agents interferes with SIRS mediated suppression of immune responses. Addition of T cells to B cell cultures stimulated with FITC-BA did not affect the total plaque forming cell response nor the extent of suppression by IFN alpha, but it did restore 2-mercaptoethanol sensitivity to IFN alpha-mediated suppression. As few as 1 X 10(5) T cells were effective and it was necessary to add T cells within 3 h of addition of IFN alpha to confer 2-mercaptoethanol sensitivity to IFN alpha mediated suppression. These data suggest that IFN alpha can suppress immune responses by two different pathways and that in the presence of T cells, activation of suppressor T cells is the dominant pathway. The presence of T cells must also prevent direct suppression of B cells by IFN alpha.