Publication: Induction of epithelial migration of
lymphocytes by intercellular adhesion molecule-1 in
a rat model of oral mucosal graft-versus-host disease
Authors
Ohno, Jun ; Iwahashi, Teruaki ; Ehara, Michiko ; Ozasa, Ryuki ; Hanada, Hironori ; Funakoshi, Tomoyuki ; Taniguchi, Kunihisa
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Publisher
Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologiam
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DOI
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info:eu-repo/semantics/article
Description
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-1expression: 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.
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