T helper cell (Th)1-primed CD4 T cells from wild-type donors make little in
terleukin (IL)-4 when restimulated under Th2 conditions. However, such rest
imulation of Th1-primed cells from interferon (IFN)-gamma (-/-) or IFN-gamm
a 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 developmen
t of IFN-gamma -producing capacity, but it plays a critical role in suppres
sing the IL-4-producing potential of Th1 cells.