SummaryTo study the factors that determine whether CD4 + T cells produce interleukin 4 (II.-4) or interferon 3' (IFN-3') upon stimulation we used a system allowing naive T cells to be primed in vitro by spedfic antigen. Dense CD4 + T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-E k. These T cells produced very limited amounts of Ib4 and IFN-3' upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/m1 IL-4, the T ceUs acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-3'. Cells primed in the absence of ID4 produced IFN-3' upon rechallenge but virtually no II.-4. The inhibitory effect of II.-4 on IFN-3' production did no appear to be mediated by the induction of Ibl0 production since IL-10 addition to initial cultures did not suppress priming for IFN-3" production, nor did anti-IL-10 block the inhibitory effect of II.-4. IFN-3' itself did not increase priming for IFN-3' production, nor did anti-IFN-3` reduce such priming. IFN-3` did, however, diminish priming for II.-4 production when limiting amounts of Ib4 (100 U/ml) were used in the initial culture. The dominant effect of Ib4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.

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