Abstract
Human small intestinal intraepithelial lymphocytes (iIEL) are a unique population of CD8alphabeta+ TCR-alphabeta+ but CD28- T lymphocytes that may function in intestinal epithelial cell immunosurveillance. In an attempt to define novel cell surface molecules involved in iIEL function, we raised several mAbs against activated iIELs derived from the small intestine that recognized an Ag on activated, but not resting, iIELs. Using expression cloning and binding studies with Fc fusion proteins and transfectants, the cognate Ag of these mAbs was identified as the N domain of biliary glycoprotein (CD66a), a carcinoembryonic Ag-related molecule that contains an immune receptor tyrosine-based inhibitory motif. Functionally, these mAbs inhibited the anti-CD3-directed and lymphokine-activated killer activity of the P815 cell line by iIELs derived from the human small intestine. These studies indicate that the expression of biliary glycoprotein on activated human iIELs and, potentially, other mucosal T lymphocytes is involved in the down-regulation of cytolytic function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / metabolism
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Antigens, CD / biosynthesis
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / immunology*
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Antigens, Differentiation / metabolism
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Carcinoembryonic Antigen
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Cell Adhesion Molecules
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Cell Line
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Cytotoxicity, Immunologic*
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Down-Regulation / immunology
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Humans
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Immunosuppressive Agents / immunology
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Immunosuppressive Agents / metabolism
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Interphase / immunology
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism
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Lymphocyte Activation
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / metabolism
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism
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Mice
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Tumor Cells, Cultured
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CD66 antigens
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Carcinoembryonic Antigen
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Ceacam1 protein, mouse
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Cell Adhesion Molecules
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Immunosuppressive Agents
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Membrane Glycoproteins