HUMAN NAIVE CD4 T-CELLS PRODUCE INTERLEUKIN-4 AT PRIMING AND ACQUIRE A TH2 PHENOTYPE UPON REPETITIVE STIMULATIONS IN NEUTRAL CONDITIONS

The maturation of naive CD4 T cells into interleukin (IL)-4-producing effecters was shown to require the presence of IL-4 at priming, the ce llular origin of which remains unclear. We demonstrate here that naive T cells themselves release IL-4 at very low levels that are neverthel ess sufficient to promote their development into Th2-like cells. This conclusion is based on three observations: (1) highly purified human n aive CD4 T cells, of neonatal or adult origin, develop into Th2 effect ers upon repetitive cycles of stimulation with anti-CD3 monoclonal ant ibody (mAb) cross-linked to CD32-B7 transfected L fibroblasts followed by IL-2 expansion; (2) IL-4 protein is readily detectable in the conc entrated supernatant fluids of priming cultures performed in the prese nce of anti-IL-4 receptor mAb; and (3) addition of anti-IL-4 or anti-I L-dr receptor mAb at priming markedly inhibits the acquisition of IL-4 - and IL-5-producing capacity while enhancing that of interferon-gamma .