Interferon-beta inhibits Th1 responses at the dendritic cell level. Relevance to multiple sclerosis.
Clinical studies have demonstrated beneficial effects of interferon-beta (IFN-beta) therapy in multiple sclerosis (MS) patients. However, the mechanism of action of IFN-beta in MS remains unknown. IFN-beta has even been demonstrated to enhance isolated T cell secretion of IFN-gamma, a cytokine proven to be deleterious in MS. However, IFN-beta inhibits IFN-gamma secretion of T cells, when they are stimulated by antigen presenting cells (APC). We therefore decided to study the effects of IFN-beta on the in vitro differentiation 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 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-beta, secreted less interleukin-12 (IL-12) both spontaneously and upon activation by CD40-ligand bearing cells. As a consequence, DC differentiated in the presence of IFN-beta induced less IFN-gamma secretion by alloreactive T cells. We conclude that the direct action of IFN-beta 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.
Bartholomé
E J
EJ
Department of Immunology, Hôpital Erasme, Brussels, Belgium.
Willems
F
F
Crusiaux
A
A
Thielemans
K
K
Schandené
L
L
Goldman
M
M
D001782:Blood Donors; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000096:biosynthesis; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D010641:Phenotype; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
D018664:Interleukin-12; D016899:Interferon-beta