Dendritic cell-derived TNF-alpha 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-alpha in generation of the IL-10-producing CD4(+) T cells by immature DCs. Immature bone marrow-derived DCs from wild type (WT) or TNF-alpha(-/-) mice were cocultured with CD4(+) T cells from OVA specific TCR transgenic mice (OT-II) in the presence of OVA(323-339) peptide. The WT DCs efficiently induced the antigen-specific IL-10-producing CD4(+) T cells, while the ability of the TNF-alpha(-/-) DCs to induce these CD4(+) T cells was considerably depressed. Addition of exogenous TNF-alpha recovered the impaired ability of the TNF-alpha(-/-) DCs to induce IL-10-producing T cells. However, no difference in this ability was observed between TNF-alpha(-/-) and WT DCs after their maturation by LPS. Thus, TNF-alpha appears to be critical for the generation of IL-10-producing CD4(+) T cells during the antigen presentation by immature DCs.