SYNERGISTIC EFFECT OF IFN-GAMMA AND TNF-ALPHA ON EXPRESSION OF IMMUNE MOLECULES AND ANTIGEN PRESENTATION BY SCHWANN-CELLS

Neonatal rat Schwann cells were characterized with regard to their immune functions in vitro. Without stimulation they displayed low levels of ICAM-1, but not of MHC class II gene products on their surface. Expression of both immune molecules was upregulated by IFN-gamma. TNF-alpha acted synergistically, but had no effect when given alone. ICAM-1 expression reached its maximum within 24 hr, whereas I-A plateaued only after 3 days of cytokine treatment. Increased expression of recognition molecules on Schwann cells correlated well with enhanced activation of CD4(+) autoimmune T cell lines between Day 1 and 2. T cell activation was blocked by adding monoclonal antibodies directed against I-A molecules, whereas ICAM-1-specific antibodies exerted a mild costimulatory effect. We conclude that Schwann cells may exert potent immunoregulatory functions by expressing MHC and adhesion molecules, which may be further upregulated by Th1-type cytokines released by immunoinflammatory T cells in the lesion. (C) 1995 Academic Press, Inc.