Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
Animals
Autopsy
Brain
/ immunology
Brain Ischemia
/ drug therapy
Cell Proliferation
Female
Humans
Immunotherapy
Integrin alpha4
/ immunology
Lymphocyte Count
Male
Mice, Inbred C57BL
Natalizumab
/ pharmacology
Neuronal Plasticity
/ drug effects
Recovery of Function
/ drug effects
Stroke
/ immunology
T-Lymphocytes
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
02 08 2021
02 08 2021
Historique:
received:
11
11
2020
revised:
31
03
2021
accepted:
28
04
2021
entrez:
26
5
2021
pubmed:
27
5
2021
medline:
3
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34037669
pii: 212190
doi: 10.1084/jem.20202411
pmc: PMC8160576
pii:
doi:
Substances chimiques
Natalizumab
0
Integrin alpha4
143198-26-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072946
Pays : United States
Informations de copyright
© 2021 Heindl et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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