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| Home > Publications Database > Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies. |
| Home > Publications Database > Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies. |
| Journal Article | DZNE-2021-01174 |
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2021
Rockefeller Univ. Press
New York, NY
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Please use a persistent id in citations: doi:10.1084/jem.20202411
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.
Keyword(s): Animals (MeSH) ; Autopsy (MeSH) ; Brain: immunology (MeSH) ; Brain: pathology (MeSH) ; Brain Ischemia: drug therapy (MeSH) ; Brain Ischemia: immunology (MeSH) ; Brain Ischemia: pathology (MeSH) ; Cell Proliferation (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Immunotherapy (MeSH) ; Integrin alpha4: immunology (MeSH) ; Lymphocyte Count (MeSH) ; Male (MeSH) ; Mice, Inbred C57BL (MeSH) ; Natalizumab: pharmacology (MeSH) ; Natalizumab: therapeutic use (MeSH) ; Neuronal Plasticity: drug effects (MeSH) ; Recovery of Function: drug effects (MeSH) ; Stroke: immunology (MeSH) ; Stroke: physiopathology (MeSH) ; Stroke: therapy (MeSH) ; T-Lymphocytes: immunology (MeSH)
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