INTERFERON 01, AN INTERMEDIATE IN THE TUMOR NECROSIS FACTOR a-INDUCED INCREASED MHC CLASS I EXPRESSION AND AN AUTOCRINE REGULATOR OF THE CONSTITUTIVE MHC CLASS I EXPRESSION

In inflammatory reactions an increased expression of HLA class I and class II antigens is observed (1). This enhanced expression is expected to play a role in the activation of both MHC class Iand class II-restricted T cells. In vitro, the mediators interferon ,8 (IFN-0), tumor necrosis factor a (TNF-a), and IFN-y induce an increase in the MHC class I expression on human umbilical venal endothelial (HUVE) cells and on human fibroblasts (2). Recombinant TNF-a has been shown to increase the mRNA level and the surface expression of MHC class I antigens via a newly synthesized protein intermediate, as wasdemonstrated in experiments using a protein synthesis inhibitor (2) . A candidate for this intermediate is IFN-#l, since IFN-01 induces an increase in MHC class I expression on HUVE cells andon human fibroblasts (2) . It has been suggested, however, that IFN-,B2 is the possible intermediate responsible for the increased MHC class I expression induced by TNFa (3). We studied the putative role of IFN-#l in the increase in MHC class I expression and the antiviral activity induced by TNF-a on HUVE cells and on human fibroblasts . Our results demonstrate that IFN-,S1 plays the major role in the rTNF-a-mediated increase in MHC class I expression and the antiviral activity . Furthermore, it was shown that IFN-#l is involved in the autocrine regulation of the constitutive MHC class I expression on HUVE cells and human fibroblasts.