T-cell replacing factor activity of recombinant-derived interleukin-2 requires gamma-interferon

In this study we show that recombinant-derived human interleukin-2 (rIL-2) has potent T-cell replacing activity in antigen-driven murine antibody responses of T-depleted spleen cells. This T-cell replacing factor (TRF) effect of rIL-2 is antigen specific. By the use of a variety of antibodies to gamma-interferon (IFN-gamma), including antibody from an interspecies hybridoma, we demonstrate that this TRF activity depends upon the production of IFN-gamma in the responding cell cultures, i.e., antibody to IFN-gamma blocks TRF activity. In addition, we show that the cell-to-cell allogeneic helper effect of T cells for antibody responses is similarly inhibited by antibodies to IFN-gamma. The inhibition of response produced by the antibodies is reversed by the addition of excess rIFN-gamma to the cultures. The results demonstrate that IFN-gamma is a necessary intermediate mediator for TRF activity mediated by IL-2 and also by T-cell-mediated help for B cells. Thus, even recombinant-derived lymphokines have complex secondary levels of action on responding cells. Antibodies to individual lymphokines are clearly a powerful resource to analyze the role of soluble factors in cellular responses.