Intercellular adhesion molecule-1 expression is required on multiple cell types for the development of experimental autoimmune encephalomyelitis.
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.
Bullard
Daniel C
DC
Department of Genetics, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
Hu
Xianzhen
X
Schoeb
Trenton R
TR
Collins
Robert G
RG
Beaudet
Arthur L
AL
Barnum
Scott R
SR
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
D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018799:Intercellular Adhesion Molecule-1