Heindl, SteffanieSteffanieHeindlRicci, AlessioAlessioRicciCarofiglio, OlgaOlgaCarofiglioZhou, QihuiQihuiZhouArzberger, ThomasThomasArzbergerLenart, NikolettNikolettLenartFranzmeier, NicolaiNicolaiFranzmeierHortobagyi, TiborTiborHortobagyiNelson, Peter T.Peter T.NelsonStowe, Ann M.Ann M.StoweDenes, AdamAdamDenesEdbauer, DieterDieterEdbauerLiesz, ArthurArthurLiesz2022-08-192022-08-192021https://resolver.sub.uni-goettingen.de/purl?gro-2/113014Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation-evading the systemic therapy-in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke.enjournal_article10.1084/jem.2020241134037669