INTERLEUKIN-12 T-CELL STIMULATING FACTOR, A CYTOKINE WITH MULTIPLE EFFECTS ON T-HELPER TYPE-1 (TH1) BUT NOT ON TH2 CELLS/

At least two subsets of CD4+ T helper cell lymphocytes termed T(h)1 an d T(h)2 exist in the mouse and probably in humans. They are characteri zed by the secretion of different lymphokines and by their functional behavior. Dysregulated expansion of one or the other subset may be one reason for the development of certain diseases. Thus, it is of import ance to define the signals involved in the differentiation and activat ion of the two T(h) cell subsets. It is known and has been confirmed i n this report that the cytokine interleukin (IL)-1 acts on T(h)2 cells but not on T(h)1 cells. We now report that a previously identified cy tokine which was provisionally termed T cell stimulating factor is ide ntical with IL-12 and exhibits a reciprocal behaviour to IL-1. IL-t2 h as several effects on T(h)1 cells. It can induce the proliferation of certain T(h)1 cells in combination with IL-2. Synthesis of interferon (IFN)-gamma by T(h)1 cells can be triggered by IL-2 plus IL-12. In con trast to the IFN-gamma production observed after T cell receptor (TcR) CD3 stimulation of T(h)1 cells with lectin Concanavalin A the IFN-gam ma production induced by IL-12 + IL-2 is insensitive to the immunosupp ressive drug cyclosporin A. Furthermore, IL-12 enhances the TcR/CD3-in duced synthesis of IFN-gamma of several T(h)1 clones. Finally, IL-12 ( + IL-2) induces homotypic cell aggregation of T(h)1 Clones. This type of cell aggregation depends on the participation of LFA-1 and ICAM-1 m olecules. In all activation systems with T(h)1 cells no effect of IL-1 was demonstrable. In contrast, only IL-1 but not IL-12 served as a co -stimulatory signal for several T(h)2 cell lines activated via the TcR /CD3 complex.