INTERLEUKIN-4 AND INTERLEUKIN-5 ARE RARELY COEXPRESSED BY HUMAN T-CELLS

Interleukin (IL)-4 and IL-5 are two cytokines which synergize in the i nduction of several biological effector functions. They are produced b y mouse and human T helper 2 (Th2) and T helper 0 (Th0) cells. Little is known about the regulation of the two cytokines at the single-cell level. Here we show, using a flow cytometric intracellular staining te chnique, that IL-4 and IL-5 are predominantly produced by different hu man peripheral CD4(+) and CD8(+) T cells, whereas interferon (IFN)-gam ma and IL-2 are produced by the same cells. In contrast, cloned human Th0 and Th2 cells were able to produce IL-4 and IL-5 simultaneously. T he segregation of IL-4 and IL-5 in activated peripheral T cells was fo und within 72 h of activation upon anti-CD3 or phorbol ester + ionomyc in stimulation. The kinetics of IL-4 and IL-5 production were differen t at the mRNA and the intra and extracellular protein level, indicatin g that the cytokines are regulated differently. T cells from three pat ients with hyper-IgE syndrome did not display a substantial proportion of IL-4/IL-5 double-positive cells. However, simultaneous production could be induced in normal human T cells after prolonged stimulation w ith a minimum of two restimulation cycles. We conclude that the simult aneous production of IL-4 and IL-5 is a feature of repetitively activa ted human T cells.