Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
J Exp Med. 2021 Aug 2;218(8):e20202411. doi: 10.1084/jem.20202411. Epub 2021 May 26. PMID: 34037669.
|Authors/Editors:||Heindl S, Ricci A, Carofiglio O, Zhou Q, Arzberger T, Lenart N, Franzmeier N, Hortobagyi T, Nelson PT, Stowe AM, Denes A, Edbauer D, Liesz A.|
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.