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@ARTICLE{Heindl:157717,
author = {Heindl, Steffanie and Ricci, Alessio and Carofiglio, Olga
and Zhou, Qihui and Arzberger, Thomas and Lenart, Nikolett
and Franzmeier, Nicolai and Hortobagyi, Tibor and Nelson,
Peter T and Stowe, Ann M and Denes, Adam and Edbauer, Dieter
and Liesz, Arthur},
title = {{C}hronic {T} cell proliferation in brains after stroke
could interfere with the efficacy of immunotherapies.},
journal = {Journal of experimental medicine},
volume = {218},
number = {8},
issn = {1540-9538},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {DZNE-2021-01174},
pages = {e20202411},
year = {2021},
abstract = {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.},
keywords = {Animals / Autopsy / Brain: immunology / Brain: pathology /
Brain Ischemia: drug therapy / Brain Ischemia: immunology /
Brain Ischemia: pathology / Cell Proliferation / Female /
Humans / Immunotherapy / Integrin alpha4: immunology /
Lymphocyte Count / Male / Mice, Inbred C57BL / Natalizumab:
pharmacology / Natalizumab: therapeutic use / Neuronal
Plasticity: drug effects / Recovery of Function: drug
effects / Stroke: immunology / Stroke: physiopathology /
Stroke: therapy / T-Lymphocytes: immunology},
cin = {AG Edbauer / AG Zhou},
ddc = {610},
cid = {I:(DE-2719)1110004 / I:(DE-2719)5000080},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34037669},
pmc = {pmc:PMC8160576},
doi = {10.1084/jem.20202411},
url = {https://pub.dzne.de/record/157717},
}