IL-6 Produced by Type I IFN DC Controls IFN-γ Production during the MLR by Blocking the Suppressive Effect of Regulatory T Cells.

The dendritic cell family is composed of different subsets able to differentially govern the immune response. Their potent antigen presenting properties make them an attractive candidate for immunization against pathogens or cancer. In that setting, the recently characterized type I IFN DCs present interesting features including a higher expression of molecules involved in antigen presentation and the ability to trigger both the cellular and humoral arms of the immune responses. In view of the pivotal role of regulatory T cells in limiting the effectiveness of effector cells, we analyzed the interactions between these cells and type I IFN DC. DC generated from monocytes in the presence of IFN-β and IL-3 (DCI3) were activated by the maturation agent poly I:C and compared with the classical myeloid DC generated in the presence of GM-CSF and IL-4 (DCG4). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-γ production by T lymphocytes during the MLR. Analysis at the mRNA level disclosed that DCI3 over transcribed the IL-6 gene leading to the release of high amounts of the protein both after the maturation process and during the MLR itself. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-γ release induced by DCI3. Finally, depletion of CD25+ T cells prior to the MLR identified these cells as a target for IL-6. We conclude from these results that DCI3 are endowed with the unique property of blocking the suppressive effect of regulatory T cells through high IL-6 production during the MLR. This novel mechanism of T cell control is relevant for the use of this DC type in vaccination strategies.