Interferon γ Enhances Both In Vitro and In Vivo Priming of CD4⁺ T Cells for IL-4 Production

Classical studies have demonstrated that in vitro priming of naive CD4 T cells to become T helper (Th)2 cells is strikingly dependent on interleukin (IL)-4, whereas priming for interferon (IFN)γ production is IL-12/IFNγ-dependent. Therefore, it was quite surprising when we noted that priming of naive C57BL/6 CD4⁺ cells to become IL-4 producers was substantially inhibited by the addition of anti-IFNγ antibodies. This was true using immobilized anti-CD3 and anti-CD28 antibodies or soluble anti-CD3/anti-CD28 and antigen-presenting cells in the presence or absence of added IL-4. Priming of CD4 T cells from IFNγ^−/− C57BL/6 mice with immobilized anti-CD3 and anti-CD28 resulted in limited production of IL-4, even with the addition of 1,000 U/ml of IL-4. Titrating IFNγ into such cultures showed a striking increase in the proportion of T cells that secreted IL-4 upon challenge; this effect was completely IL-4–dependent in that it was blocked with anti–IL-4 antibody. Thus, IFNγ plays an unanticipated but substantial role in Th2 priming, although it is an important Th1 cytokine, and under certain circumstances a Th1 inducer.