HIGH ANTIGEN DENSITY AND IL-2 ARE REQUIRED FOR GENERATION OF CD4 EFFECTORS SECRETING TH1 RATHER THAN TH0 CYTOKINES

We reevaluated the effects of Ag dose on the polarization of CD4 effec tors generated in vitro from naive pigeon cytochrome c-specific TCR tr ansgenic T cells under conditions in which we could eliminate contamin ating non-naive CD4 cells and the effects of heterogeneous Ag-presenti ng populations. When the possibility of contaminating non-naive T cell s was reduced by using T cells from transgenic mice on a RAG-2(-/-) ba ckground, Ag dose did not have a significant effect in Th1 and Th2 pol arization unless exogenous IL-2 was initially added to cultures, Effec ters generated were uniformly Th0 hut produced only IL-2 in substantia l amounts. When exogenous IL-2 was added to priming cultures, T cells secreting a Th0 phenotype (large quantities of IL-2, IL-4, IL-5, and I FN-gamma) developed, except at very high doses of Ag, where there was a striking reduction in IL-4 and IL-5 secretion. Our results imply tha t Ag dose does not have a direct effect on Th1/Th2 polarization, excep t under conditions that include a high level of TCR ligation and in th e presence of high levels of IL-2, where production of Th2 cytokines m ay be down-regulated by a mechanism that is not get clear.