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Gastroenterology Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115;
Medical Research Council, Molecular Haematology Unit, John Radcliffe Hospital, Oxford, United Kingdom;
Institut Fuer Medizinische Immunologie, Charité-Humboldt-Universität zu Berlin, Berlin, Germany;
Imperial Cancer Research Fund-Medical Oncology Unit, St. Bartholomew’s Hospital Medical College, London, United Kingdom;
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Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
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Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, and
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Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115
Human small intestinal intraepithelial lymphocytes (iIEL) are a
unique population of CD8
+ TCR-+ 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.
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