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.