Survival and cytokine polarization of naive CD4(+) T cells in vitro is largely dependent on exogenous cytokines

Naive CD4(+) T cells differ from memory cells by their heightened expressio n of the disialoceramide recognized by antibody 3G11.3G11(bright) cells res pond well to immobilized anti-CD3/anti-CD28 and to their cognate antigens b ut 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. I L-6 is particularly notable since it is neutral in regard to Th1/Th2 primin g, 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 ova lbumin 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 prod uction as a result of TCR engagement is sufficient for only a minor compone nt of the polarization observed when unseparated BALB/c CD4 T cell populati ons are primed or when IL-4 is intentionally added to the priming culture.