Distinct roles for matrix metalloproteinase-2 and alpha4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis.
Expression of alpha4 integrin by auto-reactive T cells is critical for their ability to induce EAE, an autoimmune disease of the central nervous system in mice, used as a model to study human multiple sclerosis. Having previously identified one role for alpha4 integrin in adhesion-mediated induction of matrix metalloproteinase-2 (MMP-2), an enzyme that degrades the subendothelial basement membrane matrix, we investigated independent roles for MMP-2 and alpha4 integrin during EAE. The data suggest that expression of alpha4 integrin by auto-reactive T cells is important not only in mediating MMP-2 induction to facilitate entry into the CNS, but also plays a role in maintaining residency within the CNS.
Graesser
D
D
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520, USA.
Mahooti
S
S
Madri
J A
JA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D004151:Dipeptides / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D039441:Integrin alpha4; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D001324:Autoantigens; D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D039441:Integrin alpha4; D020778:Matrix Metalloproteinase 2