IL-4 secreted from individual naive CD4+ T cells acts in an autocrine manner to induce Th2 differentiation

Naive CD4(+) T cell populations rapidly produce small amounts of IL-4 in response to T cell receptor-mediated stimulation and may undergo Th2 differentiation without exogenous IL-4. Whether this is due to autocrine IL-4-stimulation or the production of IL-4 by an infrequent naive cell has not been determined. Here we show that single CD4(+) T cells from RAG2-/- T cells receptor transgenic mice primed with their cognate antigen give rise to IL-4-producing cells at a similar frequency whether primed with or without added IL-4, but not if anti-IL-4 is added to the culture. Thus, each founder cell or one or more of its early daughters can produce sufficient IL-4 to drive Th2 differentiation. This indicates that autocrine IL-4 production by naive CD4 T cells can drive the appearance of Th2 cells.