Abstract WP142: T Cells Aggravate Intracerebral Hemorrhage Injury

Abstract

Intracerebral hemorrhage (ICH), a devastating form of stroke, has a mortality of 40% and no available treatment. Inflammation contributes to the genesis and expansion of perihematomal edema (PHE) in ICH, thus driving secondary injury and subsequent neurological deterioration. This study was carried out to elucidate contributions of lymphocytes, specifically CD4 + cells in the formation of PHE and ICH-induced neural injury. Upon examination of brain sections of ICH patients, we observed abundant CD4 + T cells among the PHE-infiltrating immune cells as early as 24 hours post-ictus. Analogous findings in ICH mouse model induced with autologous blood or collagenase injection confirmed the phenomenon. Using anti-CD4 antibody to deplete CD4 + T cells, we find that brain-infiltrating CD4 + T cells exacerbates acute ICH injury in mice by reducing BBB integrity and promoting leukocytes recruitment with early and time-dependent CD4 + T cells activation. Brain infiltrating CD4 + T cells exhibit activated transcriptome signatures, promoting local inflammation via IL-17. In the hemorrhagic brain, CD4 + T cells induces CD31 + endothelial cell apoptosis via death receptor-ligands TRAIL-DR5 pathway; specific ablation of CD4 + T cells with depleting antibody results in reduced PHE volume and improved long-term neurological outcome. In all, these data sheds new lights on T cell-mediated immune responses contributing to PHE and brain injury in ICH.