TY - JOUR
T1 - Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
AU - Heindl, Steffanie
AU - Ricci, Alessio
AU - Carofiglio, Olga
AU - Zhou, Qihui
AU - Arzberger, Thomas
AU - Lenart, Nikolett
AU - Franzmeier, Nicolai
AU - Hortobagyi, Tibor
AU - Nelson, Peter T.
AU - Stowe, Ann M.
AU - Denes, Adam
AU - Edbauer, Dieter
AU - Liesz, Arthur
N1 - Publisher Copyright:
© 2021 Heindl et al.
PY - 2021/5/26
Y1 - 2021/5/26
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20202411
DO - 10.1084/jem.20202411
M3 - Article
C2 - 34037669
AN - SCOPUS:85107071783
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
M1 - e20202411
ER -