Essential Role of Program Death 1-Ligand 1 in Regulatory T-Cell–Afforded Protection Against Blood–Brain Barrier Damage After Stroke

Background and Purpose—Our recent research revealed that adoptively transferred regulatory T cells (Tregs) reduced acute ischemic brain injury by inhibiting neutrophil-derived matrix metalloproteinase-9 (MMP-9) and protecting against blood–brain barrier damage. The mechanisms underlying Treg interactions with neutrophils remain elusive. This study evaluates the contribution of program death 1-ligand 1 (PD-L1) to Treg-mediated neutrophil inhibition and neuroprotection after cerebral ischemia. Methods—In vitro experiments were performed using a transwell system or a coculture system allowing cell-to-cell contact. Focal cerebral ischemia was induced in mice for 60 minutes. Tregs (2×106) isolated from donor animals (wild-type or PD-L1–/–) were intravenously injected into ischemic recipients 2 hours after middle cerebral artery occlusion (MCAO). MMP-9 production, blood–brain barrier permeability, and brain infarct were assessed at 1 or 3 days after MCAO. Results—In vitro experiments reveal that Treg-mediated i...