Peripheral T cells overexpress MIP-1alpha 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-1alpha (MIP-1alpha) 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-1alpha antibody. MIP-1alpha induced the expression of CCR5, a potential MIP-1alpha 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-1alpha-CCR5 interaction promoted T cells transendothelial migration via ROCK (Rho kinase). Furthermore, Abeta injection into rats' hippocampus induced MIP-1alpha overexpression accompanied with increased T lymphocytes occurrence in the brain cortex and this enhanced T cells entry was effectively blocked by anti-MIP-1alpha antibody. These data are the first to suggest that the interaction between MIP-1alpha overexpressed by T cells and CCR5 on HBMECs is involved in AD patients' T cells migrating from blood to brain.