Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (T(H)2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (T(H)1) cells express distinctive protection against infection with different pathogens. Interleukin-4 promotes the differentiation of naive CD4(+) T cells into IL-4 producers and suppresses their development into IFN-gamma producers. CD1-specific splenic CD4(+)NK1.1(+) T cells, a numerically minor population, produced IL-4 promptly on in vivo stimulation. This T cell population was essential for the induction of IL-4-producing cells and for switching to immunoglobulin E, an IL-4-dependent event, in response to injection of antibodies to immunoglobulin D.