CD4 and chemokine receptors on human brain microvascular endothelial cells, implications for human immunodeficiency virus type 1 pathogenesis

Central nervous system (CNS) dysfunction is commonly observed in children with human immunodeficiency virus type 1 (HIV-1) infection, but the mechanism(s) whereby HIV-1 causes encephalopathy remains incompletely understood. Human brain microvascular endothelial cells (HBMECs), which constitute the blood-brain barrier, are likely to contribute to HIV-1 encephalopathy, but it is unclear whether HIV-1 receptors (CD4, chemokine receptors) are present on HBMECs. In the present study, the presence of CD4 in six different children was demonstrated. Moreover, the presence of CD4 in situ on brain sections was shown. Distribution of CD4 expression was heterogeneous among microvessels; staining for CD4 was strong in some vessels and absent in other adjacent vessels. CD4 and chemokine coreceptors were found to be functional as intercellular adhesion molecule (ICAM)-l expression increased upon incubation of HBMECs with activating anti-CD4 and anti-chemokine receptor antibodies. The presence of CD4 and chemokine receptors in human brain endothelium of children may have implications for the pathogenesis of HIV-1 encephalopathy and explain the higher incidence of CNS involvement in HIV-1-infected children as compared to adults.