IL-4 is a Major Determinant of T Cell Lymphokine-Producing Phenotype

Interleukin-4 present during priming causes naive T cells from T cell receptor transgenic mice to develop into cells capable of producing IL-4 upon secondary challenge. It also suppresses the capacity of such cells to produce IL-2 and interferon gamma (IFNγ). This effect is not mediated through the action or IL-10. Priming for IL-4 production is opposed by IFNγ, but only at sub-optimal concentrations of IL-4. Different types of antigen-presenting cells display different potencies for priming but all require IL-4 to cause the development of IL-4-producing cells. Administration of anti-IL-4 at the time of in vivo priming with keyhole limpet hemocyanin (KLH) diminishes development of T cells that produce IL-4 in response to in vitro challenge with KLH for up to 75 days after immunization and diminishes the capacity of T cells to produce IL-4 after secondary in vivo challenge. By contrast, anti-IL-4 administered at the time of secondary challenge has no effect on subsequent production of IL-4. Used acutely, in vitro, IL-4 blocks accessory cell-dependent, receptor mediated IL-2 and IFNγ production. Analysis of mechanism indicates that the activated T cell is the target of IL-4 activity and that inhibition is not due to blockade of the CD28 — B7 axis or its signalling pathway. It is concluded that IL-4 is a major physiologic regulator of the differentiation of CD4+ T cells into lymphokine-producing cells. The determination of the source and the clarification of the regulation of such acute IL-4 production are key to understanding the factors that determine whether immune responses will be dominated by IL-4 or by IFNγ-producing T cells.