Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.
Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses. T cells activated by IEC are CD8+, suppressor in function, and dependent upon CD8-associated p56lck activation. A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD8+ T cell activation by IEC. Since IEC derived from patients with inflammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression. While frozen sections of normal bowel revealed bright gp180 staining on all IEC, both inflamed and uninflamed ulcerative colitis (UC) specimens showed patchy staining. In Crohn's disease (CD), staining was faint to absent. Flow cytometry confirmed immunohistochemical data. The staining patterns correlated with the ability of IEC to activate CD8-associated p56lck. Normal IEC induced phosphorylation of p56lck in CD8alpha but not CD4+ transfectants. In contrast, both UC and CD IEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional alteration of lck activation. This defect may reflect a more proximal event in the pathogenesis of IBD.
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Division of Clinical Immunology, Mount Sinai Medical Center, New York 10029, USA.
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Honig
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Mayer
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D016827:CD8 Antigens / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016827:CD8 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; C030340:elastin microfibril interface located protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)