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  • Title: High antigen density and IL-2 are required for generation of CD4 effectors secreting Th1 rather than Th0 cytokines.
    Author: Rogers PR, Huston G, Swain SL.
    Journal: J Immunol; 1998 Oct 15; 161(8):3844-52. PubMed ID: 9780149.
    Abstract:
    We reevaluated the effects of Ag dose on the polarization of CD4 effectors generated in vitro from naive pigeon cytochrome c-specific TCR transgenic T cells under conditions in which we could eliminate contaminating non-naive CD4 cells and the effects of heterogeneous Ag-presenting populations. When the possibility of contaminating non-naive T cells was reduced by using T cells from transgenic mice on a RAG-2(-/-) background, Ag dose did not have a significant effect in Th1 and Th2 polarization unless exogenous IL-2 was initially added to cultures. Effectors generated were uniformly Th0 but produced only IL-2 in substantial 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 IFN-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 that Ag dose does not have a direct effect on Th1/Th2 polarization, except under conditions that include a high level of TCR ligation and in the presence of high levels of IL-2, where production of Th2 cytokines may be down-regulated by a mechanism that is not yet clear.
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