A STRICT REQUIREMENT OF INTERLEUKIN-4 FOR INTERLEUKIN-4 INDUCTION IN ANTIGEN-STIMULATED HUMAN-MEMORY T-CELLS

The role of interleukin-4 (IL-3) in the induction of IL-4 in mouse T c ells is well established, but conflicting results have been reported w ith anti-CD3-primed human T cells and T cell clones. Therefore, IL-4 r egulation was investigated in short-term cultured human T cells primed in vitro with either a superantigen or a hapten, nickel sulfate (NiSO 4), for 3 days and expanded with IL-2 for another 5 days. Under these conditions, antigen-specific IL-3 producing T cells were generated in 35 / 40 cultures. Priming for IL-4 production was abrogated in all cul tures by anti-IL-4 antibody or soluble IL-4 receptor (sIL-SR). Primed T cells that were IL-4(-) when cultured with IL-2 only developed an IL -4 producing phenotype when primed and expanded in the presence of exo genous IL-4. T cells primed in the presence of either endogenous or ex ogenous IL-4 produced 10-200-fold more IL-4 than T cells primed in the presence of anti-IL-4 antibody or sIL-4R. While IL-4 induction was ab solutely dependent on IL-4, neither endogenous nor exogenous IL-4 infl uenced IFN-gamma synthesis. Most importantly, IL-4 induced and sIL-4R abolished priming for IL-4 production even in NiSO4-specific memory T cells from sensitized individuals. Thus, IL-4 induction in antigen-spe cific human memory T cell populations absolutely required IL-4. The IL -4 pathway of memory T cells retained a remarkable plasticity in sensi tized individuals.