An interferon-inducible molecule on brain endothelium which controls lymphocyte adhesion mediated by integrins

We undertook a search for cytokine-inducible molecules present on brain endothelium and which are involved in the control of lymphocyte adhesion. We screened 39 monoclonal antibodies (mAb) against rat brain endothelium in vitro, and identified five recognizing cytokine-inducible molecules. None of the 39 antibodies blocked lymphocyte adhesion, but one antibody (4A2), produced a 400% enhancement of lymphocyte binding. The 4A2 antigen is induced on brain endothelium by interferon-gamma (INF-gamma) but not tumour necrosis factor-alpha (TNF-alpha), at 6-48 hr. It is preferentially expressed near inter-endothelial cell junctions, but it also expressed on all lymphocytes and weakly on aortic endothelium in vitro. In vivo, it is not detectable on cells in the normal central nervous system (CNS), however it appears in the CNS during T-cell mediated immune reactions. Triggering of cells via this molecule enhances integrin-mediated adhesion of lymphocytes to brain endothelium, primarily via LFA-1. Unlike ICAM-1, 4A2 antigen is induced on endothelium of both Lewis and PVG strains. Although, it has some functional properties of human CD31, the 4A2 antigen is not rat CD31. The cellular localization of this molecule, its actions on integrin-mediated adhesion and its induction by IFN-gamma, all indicate that the 4A2 antibody recognizes a molecule involved in the control of lymphocyte migration into the brain.