title: Induction of epithelial migration of lymphocytes by intercellular adhesion molecule-1 in a rat model of oral mucosal graft-versus-host disease.
abstract: To elucidate the involvement of intercellular adhesion molecule-1 (ICAM-1) in the migration of lymphocytes to the oral mucosal epithelium in a rat model of acute graft-versus-host disease (AGVHD), we investigated (1) ICAM-1 and major histocompatibility complex (MHC) class II expression by keratinocytes (KCs) and their role in the epithelial infiltration of CD8+ cells, (2) the tissue expression of interferon-γ (IFN-γ) mRNA and expression of IFN-γ receptor by KCs, and (3) the ability of KCs to direct CD8+ cells into the epithelial layers. We classified the oral mucosal lesions into three consecutive temporal phases on the basis of increased epithelial ICAM-1 expression: basal- (phase I), parabasal- (phase II), and pan-epithelial except for the cornified cell layer (phase III). Basal ICAM-1 expression by KCs preceded that of MHC class II molecules, infiltration of CD8+ cells and epithelial histological changes. Tissue expression of IFN-γ mRNA and expression of IFN-γ receptor on KCs evidenced by immunohistochemistry were detected in early lesions (phase I), indicating that locally produced IFN-γ induced ICAM-1 expression by KCs. CD8+ cells were bound to KCs in frozen sections of epithelial lesions, whereas no lymphocyte attachment was observed in normal KC. Adherence could be inhibited by pretreating CD8+ cells with lymphocyte function-associated antigen-1 (LFA-1) antibody and/or by pretreating sections with ICAM-1 antibody. Our data suggest that in the early phase of acute oral mucosal GVHD, the induction of ICAM-1 expression on KCs leads to the migration of CD8+ cells into the epithelium and that this is mediated in part by the ICAM-1/LFA-1 pathway.
authors.affiliation: Department of Morphological Biology, Pathology Section, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, Japan. johno@college.fdcnet.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Ohno
authors.forename: Teruaki
authors.initials: T
authors.lastname: Iwahashi
authors.forename: Michiko
authors.initials: M
authors.lastname: Ehara
authors.forename: Ryuki
authors.initials: R
authors.lastname: Ozasa
authors.forename: Hironori
authors.initials: H
authors.lastname: Hanada
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D009061:Mouth Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma