Dendritic cell-derived TNF-α is responsible for development of IL-10-producing CD4+ T cells

Immature dendritic cells (DCs) appear to be involved in peripheral immune tolerance via induction of IL-10-producing CD4+ T cells. We examined the role of TNF-α in generation of the IL-10-producing CD4+ T cells by immature DCs. Immature bone marrow-derived DCs from wild type (WT) or TNF-α−/− mice were cocultured with CD4+ T cells from OVA specific TCR transgenic mice (OT-II) in the presence of OVA323–339 peptide. The WT DCs efficiently induced the antigen-specific IL-10-producing CD4+ T cells, while the ability of the TNF-α−/− DCs to induce these CD4+ T cells was considerably depressed. Addition of exogenous TNF-α recovered the impaired ability of the TNF-α−/− DCs to induce IL-10-producing T cells. However, no difference in this ability was observed between TNF-α−/− and WT DCs after their maturation by LPS. Thus, TNF-α appears to be critical for the generation of IL-10-producing CD4+ T cells during the antigen presentation by immature DCs.