INTERLEUKIN-12 INCREASES INTERLEUKIN-4 PRODUCTION BY ESTABLISHED HUMAN THO AND TH2-LIKE T-CELL CLONES

Interleukin (IL)-12 is a potent inducer of cell-mediated immunity: it favors the generation of interferon (IFN)-gamma-producing T cells, inc reases IFN-gamma production by T cells and natural killer cells and pr events the generation of a Th2 response in murine in vivo models. Neve rtheless, the effects of IL-12 on an established Th2 response remain p oorly documented. In the present paper, we analyzed the effect of IL-1 2 on the profile of lymphokines produced by established IL-4-producing Th0 and Th2-like human T cell clones (TCC) and by polyclonal T cells. We found that IL-12 (i) enhances, as previously reported, IFN-gamma p roduction by Th0 TCC and, to a smaller extent, by Th2-like TCC, (ii) i ncreases the proliferation of Th0 and Th2-like TCC and (iii) unexpecte dly, synergizes with T cell receptor-associated or nonspecific stimuli in increasing IL-4 production by these TCC. Thus, IL-12 potentiates t he production of IFN-gamma and also of IL-4 by established IL-4-produc ing TCC. Although IL-12 has been widely reported to induce a Th1 respo nse and to prevent the development of a Th2 response in vivo, IL-12 ma y on the contrary potentiate an established Th2 response in humans.