Regulation of MHC Protein Expression in Pancreatic β-Cells by Interferon-γ and Tumor Necrosis Factor-α

Publisher Website
Google Scholar
Abstract
Isolated human and mouse pancreatic islet cells and the rat insulinoma cell line RIN-m5F were used to examine the ability of recombinant interferon-.gamma. (IFN-.gamma.) and tumor necrosis factor-.alpha. (TNF-.alpha.) to regulate the expression of the class I and class II major histocompatibility (MHC) surface proteins and mRNA in .beta.-cells. Each cytokins increased significantly the expression of class I MHC proteins as determined by double indirect immunofluorescence microscopy and flow cytofluorimetric analysis. In the RIN-m5F cells, this increase in surface expressed class I MHC proteins was mirrored by an increase in the level of class I MHC mRNA. The order of potency of the cytokines on class I MHC expression was TNF-.alpha. plus IFN-.gamma. .gtoreq. IFN-.gamma. .gtoreq. TNF-.alpha.. While IFN-.gamma. or TNF-.alpha. alone were without effect, in combination they were found to induce class II MHC proteins on 30-40% of human or murine .beta.-cells. In contrast, IFN-.gamma. plus TNF-.alpha. did not induce detectable class II MHC proteins or mRNA in the RIN-m5F cells. These findings indicate that 1) TNF-.alpha., in addition to IFN-.gamma., upregulates the expression of .beta.-cell class II MHC proteins and mRNA, and 2) more than one signal is required for inducation of class II MHC proteins on .beta.-cells. The ability of IFN-.gamma. plus TNF-.alpha. to induce class II MHC proteins on only a fraction of the normal .beta.-cell population and not on RIN-m5F cells suggests that this response is related to the differentiation state of the .beta.-cell.