Using an in vitro model for the development of IFN-gamma-producing (T(
h)1) and IL-4-producing (T(h)2) cells from CD4(+) T lymphocytes expres
sing a transgenic TCR, we show that IL-12 and IL-4 are the most potent
stimuli for the differentiation of naive T cells to effector populati
ons. When combinations of cytokines are present during T cell priming,
the effect of IL-4 is dominant. Furthermore, differentiated T(h)1 cel
ls can be converted into IL-4 producers by exposure to IL-4, but the T
(h)2 phenotype is not reversible. The stability of T(h)2 populations m
ay limit the ability to regulate T(h)2-dominant responses in pathologi
c situations.