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)-γ^-/- or IFN-γ receptor (IFN-γR)^-/- mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-γ to the priming culture markedly diminished the capacity of Th1-primed IFN-γ^-/- cells to express IL-4. Even IFN-γ-producing cells from IFN-γR^-/- mice could acquire IL-4-producing capacity. Thus, IFN-γ is not required for the development of IFN-γ-producing capacity, but it plays a critical role in suppressing the IL-4-producing potential of Th1 cells.