CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium

Recent evidence suggests that interactions between CD40 on antigen presenting cells (APC) and CD40L on T cells generate signals that result in the activation of APC. In this study, the expression and function of CD40 was investigated in primary cultures of human brain microvessel endothelial cells (HBMEC). Results revealed constitutive expression of CD40 on untreated HBMEC. Stimulation with TNF-alpha, IFN-gamma, LPS or combination of TNF-alpha and IFN-gamma significantly upregulated CD40. The majority of CD40 molecules were localized on the apical surface of EC. Incubation of HBMEC with soluble CD40L resulted in increased expression of the adhesion molecules E-selectin, VCAM-1 and ICAM-1. Consequently, the adhesion of both resting and anti-CD3 activated CD4+ T lymphocytes to CD40L treated HBMEC was significantly increased compared to unstimulated EC. The expression of CD40 by cerebral endothelium, and endothelial cell activation following binding of CD40 to its ligand, CD40L, suggest a potential mechanism by which activated CD40L expressing T cells could enhance adhesion and migration of inflammatory cells across the blood-brain barrier (BBB) to sites of inflammation in the human central nervous system (CNS).