T-CELL ADHESION TO ENDOTHELIAL-CELLS AND EXTRACELLULAR-MATRIX IS MODULATED UPON TRANSENDOTHELIAL CELL-MIGRATION

During inflammation, T cells transmigrate from the bloodstream into pe rivascular tissues. As T cells transmigrate, they undergo a series of attachments to and detachments from the endothelium and then extravasa te into the extracellular matrix (ECM). T cell migration into the ECM involves a number of mechanisms that influence cell-ECM interactions. The modulation of integrin expression and affinity are two such mechan isms in which cells can alter their ability to interact with other cel ls and ECM. We show in vitro that transmigrated T cells exhibit down-r egulation of very late activation antigen-4 and leukocyte function-ass ociated antigen-1 integrin surface expression and a decrease in bindin g to recombinant vascular cell adhesion molecule-1 and recombinant int ercellular adhesion molecule-1. Also, transmigrated T cells displayed an increase in bonding to collagens I and IV and fibronectin. Further, brain sections of experimental autoimmune encephalomyelitis mice demo nstrated that as T cells migrated farther into the tissue, very late a ctivation antigen-4 expression was lost while CD4 expression remained unchanged. The significance of these findings in the modulation of the inflammatory response is discussed.