PECAM-1/CD31 expression on brain microvessel endothelium and T cells

Infiltration of CD4+ T cells into the brain is thought to be an important step in the initiation of CNS autoimmune diseases. The role of adhesion molecules in the migration of antigen-specific T cells is unclear. Platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) is involved in monocyte and neutrophil transendothelial migration, but its role in antigen(Ag)-specific T cell transendothelial migration is unknown. We examined CD31 expression on brain microvessel endothelial (En) cells and T cells and its regulation by inflammatory cytokines. FACS analysis revealed constitutive CD31 expression on murine brain microvessel En cells. When the cells were stimulated using cytokines IL-1α, TNF-α or IFN-γ for 24 to 72 hrs, CD31 was upregulated by IFN-γ and TNF-α. Using a fusion protein, PECAM-1/Ig, expression of CD31 ligand on the same En cells was also examined. We found that the ligand was upregulated by IL-1α, IFN-γ and TNF-α. CD31 is also upregulated on α/β TCR+ T cells. Ag-specific T cells were generated using PCC peptide-specific AND α/β TCR and G8 T10^b alloantigenic γ/δ TCR transgenic mice. FACS analysis revealed that Ag-specific activation of α/β TCR+ T cells produced progressive CD31 upregulation over 72 hrs whereas nonspecific activation resulted in faster but less upregulation overall. CD31 on γ/δ TCR+ T cells was unaltered. Lastly, we demonstrated localization of CD31 to contact sites between activated T cells and brain microvessel En cells. These data further suggest an important role for CD31 on brain microvessel En cells and T cells in the regulation of CNS inflammatory events.