IL-12 ACTIVATES IFN-GAMMA PRODUCTION THROUGH THE PREFERENTIAL ACTIVATION OF CD30(+) T-CELLS

CD30 is normally expressed by a subset (15 to 20%) of CD45RO(+) T cells after activation by a variety of T cell stimuli and defines the principal IFN-gamma-producing T cell subset. Inasmuch as the production of IFN-gamma is regulated by IL-2 and IL-12, we have examined the effects of these cytokines on the proliferation, induction, and function of CD30(+) and CD30(-) T cell subsets. Upon isolation, CD30(+)CD25(+) T cells exhibit high levels of baseline proliferation compared with CD30(-)CD25(+) T cells. Neutralizing Abs specific for IL-2, IL-4, IL-6, or IL-12 had no effect on basal levels of proliferation in CD30(+)CD25(+) T cells, whereas anti-IL-2 inhibited the basal proliferative activity of CD30(-)CD25(+) T cells. The addition of exogenous rIL-12 to purified CD30(+)CD25(+) and CD30(-)CD25(+) T cell subsets induced significantly higher maximal levels of proliferation in the CD30(+) subset, whereas rIL-2 supported comparable levels of maximal proliferation in each subset. The addition of rIL-1 2 to anti-CD3-activated PBMC increased the relative numbers of CD30(+) T cells by expansion of CD30(+) T cells, as opposed to recruitment of CD30(+) T cells from the CD30(-) population. Furthermore, the development of the CD30(+) T cell subset was inhibited by either anti-IL-2, anti-IL-12, or rIL-10. inhibition by anti-IL-2 and rIL-10 was overcome by the addition of rIL-12, but not IL-2, to the cultures. Finally, rIL-12 increased IFN-gamma production by CD30(+) T cells, yet had little effect on IFN-gamma production by CD30(-) T cells. Thus, CD30(+) T cells are preferentially regulated by IL-12, and the effects of IL-12 on T cell IFN-gamma production are mediated largely through its effects on the CD30(+) subset..