Induction of epithelial migration of lymphocytes by intercellular adhesion molecule-1 in a rat model of oral mucosal graft-versus-host disease

• Published in: Histology and histopathology Vol. 26; no. 6; pp. 725 - 733
• Main Authors: Ohno, Jun, Iwahashi, Teruaki, Ehara, Michiko, Ozasa, Ryuki, Hanada, Hironori, Funakoshi, Tomoyuki, Taniguchi, Kunihisa
• Format: Journal Article
• Language: English
• Published: Spain 01-06-2011
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Movement - immunology; Disease Models, Animal; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - metabolism; Graft vs Host Disease - pathology; Histocompatibility Antigens Class II - immunology; Immunohistochemistry; In Situ Hybridization; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - biosynthesis; Keratinocytes - immunology; Keratinocytes - metabolism; Mouth Mucosa - immunology; Mouth Mucosa - metabolism; Mouth Mucosa - pathology; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis
• ISSN: 1699-5848
• DOI: 10.14670/HH-26.725

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.