In differentiated CD4+ T cells, interleukin 4 production is cytokine-autonomous, whereas interferon gamma production is cytokine-dependent.

CD4+ T cells from T cell receptor transgenic mice that have been vigorously primed to be interleukin (IL)-4 producers (T(H2) cells) are capable of producing IL-4 even if restimulated in the absence of IL-4 and in the presence of IL-12. T cells vigorously primed in the absence of IL-4 (T(H1) cells) fail to produce IL-4 even if restimulated under conditions that would cause a naive T cell to produce IL-4. In contrast, interferon gamma (IFN-gamma) production is highly cytokine-regulated. T cells primed in the presence of IL-4 develop into IFN-gamma producers if IFN-gamma is included in the priming culture and if the cells are challenged in the presence of IL-12, presumably reflecting the role of IFN-gamma in inducing responsiveness to IL-12. Cells primed in the absence of IL-4 become highly responsive to IL-12 if IFN-gamma is included in the priming culture, and these cells are excellent IFN-gamma producers upon challenge; IL-12 considerably enhances their production of IFN-gamma. If cells are primed in the absence of IL-4 and IFN-gamma, they show very weak responsiveness to IL-12 as determined by STAT-4 activation. However, these cells acquire IL-12 responsiveness if cultured with IFN-gamma for a period as short as 4 hr. Thereafter, they produce large amounts of IFN-gamma upon challenge with antigen in the presence of IL-12. These results indicate that in primed CD4+ T cells, IL-4 production is largely cytokine-autonomous, whereas IFN-gamma production is highly cytokine-regulated.