Prevention of adoptive transfer of murine Sjögren's syndrome into severe combined immunodeficient (SCID) mice by antibodies against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1).
We have analysed the role of ICAM-1 and LFA-1 during development of autoimmune sialadenitis in MRL/lpr mice by direct analysis of RNA obtained from the salivary gland tissues, and the therapeutic effects with antibody administration on adoptive transfer system into SCID mice. The expression of cell adhesion molecules was assessed by using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, and immunohistochemical analysis. Up-regulated expression of ICAM-1 mRNA was observed before the onset of inflammatory lesions in the salivary glands at 1 month and 2 months old, and thereafter LFA-1 mRNA was expressed within the typical inflammatory lesions, resembling human Sjögren's syndrome in MRL/lpr mice. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of varying sized blood vessels before the onset of disease, and LFA-1 expressing inflammatory cells were found within these lesions. When the therapeutic effects in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented adoptive transfer of Sjögren's syndrome in MRL/lpr mice into SCID mice, while no significant effect was found when treated with either antibody. These findings indicate that in Sjögren's syndrome-like autoimmune lesions in MRL/lpr mice the ICAM-1/LFA-1 pathway may play a crucial role in the initiation and subsequent progression of T cell-mediated autoimmunity in the salivary and lacrimal glands of MRL/lpr mice.
Hayashi
Y
Y
Department of Pathology, Tokushima University School of Dentistry, Japan.
Haneji
N
N
Yanagi
K
K
Higashiyama
H
H
Yagita
H
H
Hamano
H
H
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D007116:Immunization, Passive; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID / Q000276:immunology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012793:Sialadenitis / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000517:prevention & control
D017931:DNA Primers; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1