INTERFERON-BETA-1B REDUCES INTERFERON GAMMA-INDUCED ANTIGEN-PRESENTING CAPACITY OF HUMAN GLIAL AND B-CELLS

Interferon (IFN) beta-1b has been shown to alter the course of multiple sclerosis and to inhibit MHC class II expression, but its effect on antigen presentation has not been examined in a functional assay (Neurology 43 (1993) 655-661). The effect of IFN beta-1b on alloantigen presentation by human antigen-presenting cells (APC) including human fetal astrocytes (HFA) and microglia was examined. The effect of IFN beta-1b on the ability of B cells to present tetanus toroid (TT) to TT-specific T cell lines was also examined. APC were pre-treated with IFN gamma (100 units/ml), IFN beta-1b (10-2000 units/ml), or a combination of IFN gamma and IFN beta-1b for 3 days and washed thoroughly prior to culture with allogeneic peripheral blood lymphocytes (PBL) for a period of 6 days. Lymphocyte proliferation was then measured by tritiated thymidine uptake. Treatment of the APC with IFN beta-1b resulted in a reduction in the IFN gamma-enhanced alloantigen-induced T cell responses. This reduction ranged between 50 and 70%, was associated with a 30-50% reduction in HLA class II (DR) and 35-40% reduction in ICAM-1 expression on the HFA used as APC. IFN beta-1b pretreatment of B cells reduced their constitutive and IFN gamma enhanced capacity to present TT to TT-specific T cell lines by 50-80%. This was associated with a 30 +/- 11% mean reduction in class II (DR) expression and approximately 50 +/- 1% reduction in ICAM-1 expression in IFN beta-1b + IFN gamma-treated B cells compared to IFN gamma-treated B cells (mean of three experiments). The reduction in antigen presentation and class II expression was not due to cellular toxicity as cell viability and tritiated thymidine uptake by APC were not altered significantly with treatment. The results suggest that IFN beta-1b can downregulate antigen presentation which could be related to altered expression of cell surface molecules on the APC and possibly also an effect on antigen processing.