Interferon-beta inhibits Th1 responses at the dendritic cell level - Relevance to multiple sclerosis

Clinical studies have demonstrated beneficial effects of interferon-beta (I FN-beta) therapy in multiple sclerosis (MS) patients. However, the mechanis m of action of IFN-beta in MS remains unknown. IFN-beta has even been demon strated to enhance isolated T cell secretion of IFN-gamma. a cytokine prove n to be deleterious in MS. However, IFN-beta inhibits IFN-gamma secretion o f T cells, when they are stimulated by antigen presenting cells (APC). We t herefore decided to study the effects of IFN-beta on the in vitro different iation of dendritic cells (DC), a major class of APC. First, we found that the addition of IFN-beta at the initiation of the differentiation did not m odify DC morphology, but enhanced the expression of molecules involved in a ntigen presentation (HLA-DR, B7/1 and B7/2). However, DC, differentiated in the presence of IFN-beta, secreted less interleukin-12 (IL-12) both sponta neously and upon activation by CD40-ligand bearing cells. As a consequence, DC differentiated in the presence of IFN-beta induced less IFN-gamma secre tion by alloreactive T cells. We conclude that the direct action of IFN-bet a on DC results in inhibition of their ability to secrete IL-12 and to elic it Thelper-1 (Th-1) type responses. These results are of particular interes t in MS, in which a critical role for IL-12 has recently been suggested by a number of clinical and experimental observations.