TY  - JOUR
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
TI  - Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
JO  - Journal of experimental medicine
VL  - 218
IS  - 8
SN  - 1540-9538
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DZNE-2021-01174
SP  - e20202411
PY  - 2021
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.
KW  - Animals
KW  - Autopsy
KW  - Brain: immunology
KW  - Brain: pathology
KW  - Brain Ischemia: drug therapy
KW  - Brain Ischemia: immunology
KW  - Brain Ischemia: pathology
KW  - Cell Proliferation
KW  - Female
KW  - Humans
KW  - Immunotherapy
KW  - Integrin alpha4: immunology
KW  - Lymphocyte Count
KW  - Male
KW  - Mice, Inbred C57BL
KW  - Natalizumab: pharmacology
KW  - Natalizumab: therapeutic use
KW  - Neuronal Plasticity: drug effects
KW  - Recovery of Function: drug effects
KW  - Stroke: immunology
KW  - Stroke: physiopathology
KW  - Stroke: therapy
KW  - T-Lymphocytes: immunology
LB  - PUB:(DE-HGF)16
C6  - pmid:34037669
C2  - pmc:PMC8160576
DO  - DOI:10.1084/jem.20202411
UR  - https://pub.dzne.de/record/157717
ER  -