Neuroinflammation 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.
Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
Disclosures: The authors declare no competing interests exist.
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Steffanie Heindl, Alessio Ricci, Olga Carofiglio, Qihui Zhou, Thomas Arzberger, Nikolett Lenart, Nicolai Franzmeier, Tibor Hortobagyi, Peter T. Nelson, Ann M. Stowe, Adam Denes, Dieter Edbauer, Arthur Liesz; Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies. J Exp Med 2 August 2021; 218 (8): e20202411. doi: https://doi.org/10.1084/jem.20202411
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