IL-6 produced by type I IFN DC controls IFN-gamma production by regulating the suppressive effect of CD4+ CD25+ regulatory T cells

Abstract

The dendritic cell family is composed of different subsets differentially governing the immune response. Type I interferon (IFN) dendritic cells (DC) are endowed with the ability to trigger both Th1 and Th2 type 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 were generated from monocytes in the presence of IFN-beta and interleukin (IL)-3 (DCI3) or granulocyte macrophage-colony-stimulating factor and IL-4 (DCG4) and activated by poly(I:C). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-gamma production by T lymphocytes during the mixed leucocyte reaction (MLR) as compared with DCG4. mRNA analysis disclosed that DCI3 overtranscribed the IL-6 gene and secreted high amounts of the protein. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-gamma release induced by DCI3. Finally, depletion of CD25+ T cells before the MLR identified these cells as a target for IL-6. We conclude that DCI3 are endowed with the property of regulating the suppressive effect of regulatory T cells through high IL-6 production. This novel mechanism of T cell control is relevant for the use of DCI3 in vaccination strategies.