The expression and regulation of class II antigens in normal and inflammatory bowel disease peripheral blood monocytes and intestinal epithelium.
Elevated constitutive expression of major histocompatibility (MHC) class II antigens occurs in the enterocytes of patients with IBD. It has been suggested that this aberrant expression of class II molecules may play a role in the pathogenesis of IBD. We examined two possible reasons for such a finding. 1) Heightened sensitivity of IBD enterocytes to endogenous gamma interferon (gamma IFN) and 2) enhanced endogenous secretion of gamma interferon by intestinal cells in close proximity to the enterocytes (lamina propria lymphocytes). Constitutive and gamma interferon stimulated HLA-DR and DP density on intestinal epithelial cells (IEC) and peripheral blood monocytes (PBM) from UC patients (IEC n = 13; PBM n = 20), CD patients (IEC n = 14; PBM n = 18) and non-IBD controls (IEC n = 12; PBM n = 20) were measured via flow cytometry (mean channel fluorescence). gamma IFN production by PHA stimulated and unstimulated lamina propria lymphocyte (LPL) cultures of UC patients (n = 11) CD patients (n = 8) and non-IBD controls (n = 11) was measured using a vesicular stomatitis virus/WISH cell bioassay. We found significantly greater gamma IFN secretion by IBD-derived PHA stimulated LPL than from non-IBD stimulated controls (CD = 39.4 +/- 12.4u; UC41.5 +/- 6.8u; NL = 22.4 +/- 8.3u, p less than 0.05) while gamma IFN induced HLA-DR and DP upregulation was no greater in IBD-derived IEC and PBM than in non-IBD controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Clinical Immunology, Mount Sinai School of Medicine, Mount Sinai Hospital, New York, NY 10029.
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P
Salomon
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Pizzimenti
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Panja
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Reisman
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Mayer
D001249:Asthma / Q000276:immunology; D015551:Autoimmunity; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006682:HLA-DP Antigens / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*
D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma