Experimental autoimmune encephalomyelitis in intercellular adhesion molecule-1-deficient mice.
Intercellular adhesion molecule (ICAM)-1, or CD54, is a member of the immunoglobulin superfamily that binds to lymphocyte function-associated antigen-1 and macrophage-1 antigen. ICAM-1:LFA-1/Mac-1 interaction may be involved in both activation and extravasation of leukocytes. To determine the roles of ICAM-1 in the development of autoimmune disease, we studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in ICAM-1. We found that T cell proliferation and TH1-type cytokine production in response to myelin antigen were significantly reduced in ICAM-1-deficient mice, whereas TH2-type cytokine IL-10 was increased. Unexpectedly, EAE induced by either myelin oligodendrocyte glycoprotein or myelin basic protein was significantly enhanced in mice deficient in ICAM-1. The enhancement was evidenced primarily by the increase in disease severity, mortality, and the degree of central nervous system inflammation. The cellular composition of the inflammatory infiltrates in the central nervous system is similar in control and ICAM-1-deficient mice. These results suggest that (1) ICAM-1 is involved in the activation of autoreactive TH-1, but not TH2 cells, and (2) ICAM-1 plays an important role in down-regulating autoimmune inflammation in the central nervous system.
Samoilova
E B
EB
Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.
Horton
J L
JL
Chen
Y
Y
D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
D004676:Myelin Basic Protein; D018799:Intercellular Adhesion Molecule-1