%0 Journal Article
%A Heindl, Steffanie
%A Ricci, Alessio
%A Carofiglio, Olga
%A Zhou, Qihui
%A Arzberger, Thomas
%A Lenart, Nikolett
%A Franzmeier, Nicolai
%A Hortobagyi, Tibor
%A Nelson, Peter T
%A Stowe, Ann M
%A Denes, Adam
%A Edbauer, Dieter
%A Liesz, Arthur
%T Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
%J Journal of experimental medicine
%V 218
%N 8
%@ 1540-9538
%C New York, NY
%I Rockefeller Univ. Press
%M DZNE-2021-01174
%P e20202411
%D 2021
%X 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.
%K Animals
%K Autopsy
%K Brain: immunology
%K Brain: pathology
%K Brain Ischemia: drug therapy
%K Brain Ischemia: immunology
%K Brain Ischemia: pathology
%K Cell Proliferation
%K Female
%K Humans
%K Immunotherapy
%K Integrin alpha4: immunology
%K Lymphocyte Count
%K Male
%K Mice, Inbred C57BL
%K Natalizumab: pharmacology
%K Natalizumab: therapeutic use
%K Neuronal Plasticity: drug effects
%K Recovery of Function: drug effects
%K Stroke: immunology
%K Stroke: physiopathology
%K Stroke: therapy
%K T-Lymphocytes: immunology
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34037669
%2 pmc:PMC8160576
%R 10.1084/jem.20202411
%U https://pub.dzne.de/record/157717