Interferon‐γ in vivo. Induction and loss of class IIMHC antigens and immature myelomonocytic cells in rat organs

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Abstract
The effects of recombinant rat interferon-y on class II major histocompatibility complex antigen expression in vivo were studied by immunohistology in LEW rats after continuous intravenous infusion for three days. Interferon-γ administration led to a systemic induction of class II molecules in previously negative parenchymal and stromal cells. The induction patterns observed were highly reproducible, but not closely dose dependent within a 25-fold dose difference tested. However, the effect of interferon infusion differed profoundly in individual cell types, and appeared to be related to the differentiation stage of each cell- population. Thus, epithelial cells like duct epithelia, urothelium or basal ear skin keratinocytes as well as endothelia in big vessels were strongly and easily induced for class II antigen expression. Parenchymal cells like cardiomyocytes and hepatocytes showed intermediate reactivity, while capillary endothelia, neurons in the brain, straight proximal kidney tubules or endocrine pancreatic islet cells did not express class II antigens. The induced expression was rapidly lost from most cells within one or two days after interferon withdrawal; the only exception occurred in keratinocytes. Long-term alterations were, however, still found 14 days after infusion. Interstitial class II-positive dendritic-shaped cells were increased in the organs and hepatic Kupffer cells carried class II antigens. On conventional histology all organs appeared perfectly normal at this date. After three days of interferon, cells of an immature myelomonocytic phenotype occluded medium-sized and small veins in all organs and occurred in granuloma-like lesions in the liver. Although these cells quickly disappeared after interferon withdrawal they might have been at least partially responsible for single deaths on day three. Our study provides a basis for testing the immunological in vivo function of parenchymal class II antigen expression and its differentiation-specific regulation.