Peripheral T cells overexpress MIP-1α to enhance its transendothelial migration in Alzheimer's disease

Abstract 

It is unclear how circulating T cells cross the blood–brain barrier (BBB) and participate in the inflammation process in Alzheimer's disease (AD). Here we showed significantly higher macrophage inflammatory protein-1α (MIP-1α) expression in peripheral T lymphocytes of AD patients than age-matched controls. T cells crossing of the human brain microvascular endothelial cells (HBMECs) which constitute the BBB, were almost completely abrogated by anti-MIP-1α antibody. MIP-1α induced the expression of CCR5, a potential MIP-1α receptor, on HBMECs. HBMECs tranfected with CCR5 resulted in increased T cells transendothelial migration. CCR5 antagonist (2D7 mAb) blocked the T cells transmigration. The MIP-1α–CCR5 interaction promoted T cells transendothelial migration via ROCK (Rho kinase). Furthermore, Aβ injection into rats’ hippocampus induced MIP-1α overexpression accompanied with increased T lymphocytes occurrence in the brain cortex and this enhanced T cells entry was effectively blocked by anti-MIP-1α antibody. These data are the first to suggest that the interaction between MIP-1α overexpressed by T cells and CCR5 on HBMECs is involved in AD patients’ T cells migrating from blood to brain.

Keywords: Alzheimer's disease, Amyloid beta, T cell, MIP-1α, CCR5, Blood–brain barrier, Brain endothelial cells, Tight junction