CYTOKINE-REGULATED ADHESION BETWEEN ENCEPHALITOGENIC T-LYMPHOCYTES AND CEREBROVASCULAR ENDOTHELIAL-CELLS

Adhesive interactions between murine cerebrovascular endothelial cells (EC) which comprise the blood-brain barrier (BBB) and myelin basic protein (MBP)-specific encephalitogenic T lymphocytes were investigated. Adhesion was assessed by measuring the percent attachment of Cr-51-labeled T cells to EC monolayers. The basal level adhesion (20-35%) was significantly up-regulated by treating EC with recombinant murine gamma interferon (IFN-gamma), interleukin-1alpha (IL-1alpha) and/or tumor necrosis factor-alpha (TNFalpha). The ability of these cytokines to modulate adhesion was dose- and time-dependent and could be detected as early as 1 h after treatment. The expression of intercellular adhesion molecule-1 (ICAM-1) by EC was examined by immunofluorescence staining and ELISA. Although all unstimulated EC cultures expressed ICAM-1, treatment of EC with the above cytokines dramatically up-regulated the level of ICAM-1 expression in a dose- and time-dependent fashion similar to that observed in the adhesion assays. Treatment of EC with transforming growth factor-beta1 (TGFbeta) down-regulated the level of T cell adhesion on untreated EC in a dose-dependent manner. Pretreatment of EC with TGFbeta also partially inhibited the up-regulation of adhesion induced by IFN-gamma, IL-1alpha and/or TNFalpha. TGFbeta had no effect on the up-regulation of ICAM-1 expression induced by IFN-gamma, IL-1alpha and/or TNFalpha. These results indicate that in addition to ICAM-1, other molecules may be involved in adhesion of encephalitogenic T cells to the EC comprising the cerebral vasculature. Such interactions are believed to be important to the migration of cells across the BBB and development of inflammatory lesions in the central nervous system (CNS).