Distinct roles for matrix metalloproteinase-2 and alpha 4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis

Expression of alpha 4 integrin by auto-reactive T cells is critical for the ir ability to induce EAE, an autoimmune disease of the central nervous syst em in mice, used as a model to study human multiple sclerosis. Having previ ously identified one role for alpha 4 integrin in adhesion-mediated inducti on of matrix metalloproteinase-2 (MMP-2), an enzyme that degrades the suben dothelial basement membrane matrix, we investigated independent roles for M MP-2 and alpha 4 integrin during EAE. The data suggest that expression of a lpha 4 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. (C) 2000 Elsevier Science B.V. All r ights reserved.