INTERLEUKIN-4 SUPPRESSES INTERLEUKIN-2 AND INTERFERON-GAMMA PRODUCTION BY NAIVE T-CELLS STIMULATED BY ACCESSORY CELL-DEPENDENT RECEPTOR ENGAGEMENT

Interleukin 2 (IL-2) and interferon gamma (IFN-gamma) production by CD 4+ T cells and IFN-gamma production by CD8+ T cells from naive mice in response to soluble anti-CD3 and antigen-presenting cells (APCs) were strikingly inhibited by culture in the presence of IL-4. IL-4 decreas ed IL-2 and IFN-gamma mRNA levels after 15-24 hr but gave relatively l ittle decrease in these mRNAs at 6-12 hr after stimulation with solubl e anti-CD3. A 16-hr preculture of T cells with anti-CD3, APCs, and IL- 4 was sufficient to inhibit subsequent production of IL-2 and IFN-gamm a in response to restimulation in the absence of IL-4. Furthermore, IL -4 treatment of T cells purified 24 hr after stimulation inhibited the ir capacity to subsequently produce IL-2 in response to anti-CD3 and A PCs, indicating that T cells were targets of IL-4-mediated inhibition. IL-4 blocked acute IL-2 production in response to a cytochrome c pept ide of T cells derived from transgenic mice expressing T-cell receptor s specific for cytochrome c but it did not block IL-2 production by su ch cells after they had been primed in vitro. Nor did IL-4 inhibit pro duction of IFN-gamma by cloned T cells in response to antigen and APCs or production of IL-2 and IFN-gamma by naive T cells in response to p horbol ester and calcium ionophore. These results indicate that IL-4 s trikingly inhibits IL-2 and IFN-gamma production by naive T cells in r esponse to accessory cell-dependent, receptor-mediated stimulation (i. e., soluble anti-CD3 and APCs or antigen and APCs) but does not inhibi t accessory cell-independent stimulation of naive T cells or accessory cell-dependent receptor-mediated stimulation of recently primed T cel ls or cloned T-cell lines.