Identification of an adhesion molecule expressed on adult T cell leukemia cells derived from a patient with gastrointestinal involvement: implication for a possible role of integrin beta 7 in leukemic cell infiltration into intestinal mucosa.
Patients with adult T cell leukemia (ATL) often manifest leukemic cell infiltration into various organs such as lung, liver, skin, and gut. To analyze the mechanism of intestinal infiltration of ATL cells, we made mAbs against ATL-43T, a human T cell line derived from an ATL patient with severe intestinal mucosal infiltration. One of the mAbs, named H920, was noted for a high and relatively specific reactivity with ATL-43T. Molecular cloning was done to identify this molecule and disclosed that the Ag molecule was identical to integrin beta 7. Since integrin beta 7 and its ligand MAdCAM-1 had been reported to mediate homing of lymphocytes to endothelial cells in intestinal mucosa, we next examined wither ATL-43T cells could adhere to MAdCAM-1+ cells. Human MAdCAM-1 transfectants of MMCE, a mouse epithelial cell line, were made and used to evaluate cell adhesion mediated by integrin beta 7 and MAdCAM-1. Considerable levels of cell adhesion were observed between ATL-43T and the transfectant cells, which was inhibited by H920 mAb in a dose-dependent manner. Furthermore, peripheral blood leukemic cells or lymphoma cells from 10 ATL patients were examined for expression of integrin beta 7 with regard to organ involvement. Samples from three patients with gastrointestinal tract involvement showed considerably higher expression of integrin beta 7. These results suggest that integrin beta 7 may play a role in adhesion and subsequent infiltration of a certain type of ATL cells into intestinal mucosa.
Department of Virus Immunology, Kyoto University, Japan.
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H
Chen
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Hori
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M
Maeda
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Uchiyama
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D019921:Biotinylation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D039641:Integrin beta Chains; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology*; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology*; D017254:Leukemic Infiltration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009088:Mucoproteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; D016023:Integrins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C091368:integrin beta7