Interferon γ stabilizes the T helper cell type 1 phenotype

T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-gamma (-/-) or IFN-gamma receptor (IFN-gammaR)(-/-) mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-gamma to the priming culture markedly diminished the capacity of Th1-primed IFN-gamma (-/-) cells to express IL-4. Even IFN-gamma -producing cells from IFN-gammaR(-/-) mice could acquire IL-4-producing capacity. Thus, IFN-gamma is not required for the development of IFN-gamma -producing capacity, but it plays a critical role in suppressing the IL-4-producing potential of Th1 cells.