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

par Bartholomé, Emmanuel ;Willems, Fabienne ;Crusiaux, Alain;Thielemans, Kris M.;Schandené, Liliane ;Goldman, Michel
Référence Acta neurologica belgica, 99, 1, page (44-52)
Publication Publié, 1999-03

Article révisé par les pairs

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Résumé :

Clinical studies have demonstrated beneficial effects of interferon-β (IFN-β) therapy in multiple sclerosis (MS) patients. However, the mechanism of action of IFN-β in MS remains unknown. IFN-β has even been demonstrated to enhance isolated T cell secretion of IFN-γ, a cytokine proven to be deleterious in MS. However, IFN-β inhibits IFN-γ secretion of T cells, when they are stimulated by antigen presenting cells (APC). We therefore decided to study the effects of IFN-β on the in vitro differentiation of dendritic cells (DC), a major class of APC. First, we found that the addition of IFN- β at the initiation of the differentiation did not modify DC morphology, but enhanced the expression of molecules involved in antigen presentation (HLA- DR, B7/1 and B7/2). However, DC, differentiated in the presence of IFN-β, secreted less interleukin-12 (IL-12) both spontaneously and upon activated by CD40-ligand bearing cells. As a consequence, DC differentiated in the presence of IFN-β induced less IFN-γ secretion by alloreactive T cells. We conclude that the direct action of IFN-β on DC results in inhibition of their ability to secrete IL-12 and to elicit Thelper-1 (Th-1) type responses. These results are of particular interest in MS, in which a critical role for IL-12 has recently been suggested by a number of clinical and experimental observations.