In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 218, No. 8 ( 2021-08-02)
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.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20202411
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2021
detail.hit.zdb_id:
1477240-1
Permalink