IGIF DOES NOT DRIVE TH1 DEVELOPMENT BUT SYNERGIZES WITH IL-12 FOR INTERFERON-GAMMA PRODUCTION AND ACTIVATES IRAK AND NF-KAPPA-B

In these studies, IFN gamma-inducing factor (IGIF), unlike IL-12, did not drive Th1 development in BALB/c or C57Bl/6 mice, but like IL-1 alp ha, potentiated IL-12-driven Th1 development in BALB/c mice. IGIF and IL-12 synergized for IFN gamma production from Th1 cells. Unlike IL-1 alpha, IGIF had no effect on Th2 cells. IGIF signaled through IRAK, IL -1 receptor-associated kinase, to induce nuclear translocation of p65/ p50 NFB in Th1 cells. IL-1 alpha had no effect on proliferation, cytok ine production, or NFKB activation in Th1 cells but activated NFKB and proliferation in Th2 cells. Thus, Th1 and Th2 cells may differ in res ponsiveness and receptor expression for IL-1 family molecules. IGIF an d IL-1 alpha may differentially amplify Th1 and Th2 effector responses , respectively.