Regulation of Th1 and Th2 lymphocyte migration by human adult brain endothelial cells

Endothelial cells of the blood-brain barrier (BBB) have the ability to regu late and restrict the passage of cells and molecules from the periphery to the CNS. We have used an in vitro assay of lymphocyte migration across mono layers of human adult brain endothelial cells (HBEC) as a model of lymphocy te migration across the BBB. We found that human allogeneic or MBP-reactive Th2-polarized lymphocytes mi.-rate more avidly than Th1-polarized lymphocy tes. Migration of Th2 but not Th1 cells across brain endothelium was inhibi ted by antibodies directed at MCP-1, a chemokine produced by HBECs. We coul d detect CCR2, a chemokine receptor that recognizes MCP-1 on Th2 but not Th 1 lymphocytes. ICAM-1 and VCAM-1 molecules were expressed on the surface of HBECs under basal conditions and were upregulated by Th1 but not Th2 cell- derived supernatants. Migration of both lymphocyte subsets was dependent on LFA-1/ICAM-1 interactions. Blocking VLA-4/VCAM-1 binding did not influence actual trans-endothelial mi.-ration. These results suggest that HBECs comp osing the BBB favor the mi.-ration of Th2 cells. We postulate that this sel ectivity may help prevent activated Th1 lymphocytes, the putative CNS autoi mmune disease initiating cells, from reaching the CNS parenchyma and favor entry of Th2 cells, a putative means to induce bystander suppression in the CNS.