Naive CD4(+) T cells differ from memory cells by their heightened expression of the disialoceramide recognized by antibody 3G11. 3G11(bright) cells respond well to immobilized anti-CD3 / anti-CD28 and to their cognate antigens but produce little or no IFN-gamma or IL-4 "acutely" and undergo cell death even in the presence of IL-2. They can be rescued by IL-4, IL-6 or IL-12. IL-6 is particularly notable since it is neutral in regard to Th1 / Th2 priming, allowing an assessment of the role of endogenous IL-4 in priming for IL-4 production. Naive TCR-transgenic BALB / c scid T cells cultured with an ovalbumin peptide and IL-4(- / -) antigen-presenting cells in the presence of IL-6 showed a modest degree of priming for IL-4 production if both IFN-gamma and IL-12 were neutralized. This priming is far less than that observed if IL-4 is added to the priming culture. These results indicate that IL-4 production as a result of TCR engagement is sufficient for only a minor component of the polarization observed when unseparated BALB / c CD4 T cell populations are primed or when IL-4 is intentionally added to the priming culture.