title: Intercellular adhesion molecule-1 expression is required on multiple cell types for the development of experimental autoimmune encephalomyelitis.
abstract: Many members of the Ig superfamily of adhesion molecules, such as ICAM-1 and VCAM-1, have been implicated in the pathogenesis of multiple sclerosis. Although it is well-established that VCAM-1/VLA-4 interactions can play important roles in mediating CNS inflammatory events in multiple sclerosis patients and during the development of experimental allergic encephalomyelitis (EAE), the contributions of ICAM-1 are poorly understood. This is due in large part to conflicting results from Ab inhibition studies and the observation of exacerbated EAE in ICAM-1 mutant mice that express a restricted set of ICAM-1 isoforms. To determine ICAM-1-mediated mechanisms in EAE, we analyzed ICAM-1 null mutant mice (ICAM-1(null)), which express no ICAM-1 isoforms. ICAM-1(null) mice had significantly attenuated EAE characterized by markedly reduced spinal cord T cell infiltration and IFN-gamma production by these cells. Adoptive transfer of Ag-restimulated T cells from wild-type to ICAM-1(null) mice or transfer of ICAM-1(null) Ag-restimulated T cells to control mice failed to induce EAE. ICAM-1(null) T cells also showed reduced proliferative capacity and substantially reduced levels of IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-12 compared with that of control T cells following myelin oligodendrocyte glycoprotein 35-55 restimulation in vitro. Our results indicate that ICAM-1 expression is critical on T cells and other cell types for the development of demyelinating disease and suggest that expression of VCAM-1 and other adhesion molecules cannot fully compensate for the loss of ICAM-1 during EAE development.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.forename: Robert G
authors.initials: RG
authors.lastname: Collins
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein
chemical_list: D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018799:Intercellular Adhesion Molecule-1