Human naive CD4 T cells produce interleukin‐4 at priming and acquire a Th2 phenotype upon repetitive stimulations in neutral conditions

Abstract

The maturation of naive CD4 T cells into interleukin (IL)‐4‐producing effectors was shown to require the presence of IL‐4 at priming, the cellular origin of which remains unclear. We demonstrate here that naive T cells themselves release IL‐4 at very low levels that are nevertheless sufficient to promote their development into Th2‐like cells. This conclusion is based on three observations: (1) highly purified human naive CD4T cells, of neonatal or adult origin, develop into Th2 effectors upon repetitive cycles of stimulation with anti‐CD3 monoclonal antibody (mAb) cross‐linked to CD32‐B7 transfected L fibroblasts followed by IL‐2 expansion; (2) IL‐4 protein is readily detectable in the concentrated supernatant fluids of priming cultures performed in the presence of anti‐IL‐4 receptor mAb; and (3) addition of anti‐IL‐4 or anti‐IL‐4 receptor mAb at priming markedly inhibits the acquisition of IL‐4‐ and IL‐5‐producing capacity while enhancing that of interferon‐γ.