CROSSREGULATION BETWEEN T-HELPER CELL (TH)1 AND TH2 - INHIBITION OF TH2 PROLIFERATION BY IFN-GAMMA INVOLVES INTERFERENCE WITH IL-1

The Th1-derived cytokine IFN-gamma inhibits the proliferation of Th2 l ymphocytes, but the mechanism of inhibition is not known. Under certai n disease conditions, an established Th2-mediated immune response is u ndesirable and a Th1-mediated response is beneficial. However, establi shed Th2 cells appear to be phenotypically stable. Thus, learning more about cytokine-mediated regulation of established Th2 cells is import ant if deleterious immune responses are to be altered, We studied the effects of IFN-gamma on a panel of recently derived Th2 lines and clon es, as well as a previously established Th2 clone, 13.26. Inhibition b y IFN-gamma was observed only when there was a concomitant response to IL-1, a known costimulator of Th2. Clone 13.26 was particularly sensi tive to both IL-1 and IFN-gamma, so it was studied in greater detail. We examined cytokine responses using stimulation by anti-TCR mAb-coate d plates, or Ag presented by APC populations that do or do not produce IL-1. All IL-1-mediated proliferative responses of 13.26 were inhibit ed by IFN-gamma, whereas IL-1-independent (IL-4-associated) responses were unaffected. Our data suggest that IFN-gamma inhibits Th2 prolifer ation through an IL-1-dependent mechanism, and furthermore, that the c ostimulatory pathways used by APCs may be critical for subsequent Th c ell responses to cytokines.