Interferon-lambda-treated Dendritic Cells Specifically Induce Proliferation of FOXP3-expressing Suppressor T Cells

The lambda interferons (IFN-lambdas), also known as IL-28 and IL-29, are coexpressed with IFN-beta after Toll-like-receptor (TLR) stimulation in human monocyte-derived dendritic cells (DCs). IFN-lambda shares with type I IFNs an intracellular signaling pathway that drives the expression of a common set of genes. However, IFN-lambda signaling is initiated through a membrane receptor system distinct from that of type I IFNs. Because IFNs produced by DCs in response to TLR stimulation are critical in the differentiation and maturation of DCs, we sought to investigate whether IFN-lambda exhibits specific effects on DC differentiation. In this work, we show that DCs acquire IFN-lambda responsiveness through the expression of the specific IFN-lambda receptor chain during their differentiation from monocytes. IFN-lambda-treated DCs express high levels of major histocompatibility complex class I (MHC class I) and MHC class II but low levels of costimulatory molecules. However, they express CCR7 and acquire the ability to migrate to lymph nodes when intravenously injected into SCID/Bg mice. In mixed lymphocyte reaction (MLR) cultures, IFN-lambda-treated DCs specifically induced IL-2-dependent proliferation of a CD4(+)CD25(+)Foxp3(+) T-cell subset with contact-dependent suppressive activity on T-cell proliferation initiated by fully mature DCs. IFN-lambdas are thus able to generate tolerogenic DCs, an activity that could thwart IFN-beta functions.