Open AccessChronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
Author(s) -
Steffanie Heindl,
Alessio Ricci,
Olga Carofiglio,
Qihui Zhou,
Thomas Arzberger,
Nikolett Lénárt,
Nicolai Franzmeier,
Tibor Hortobágyi,
Peter T. Nelson,
Ann M. Stowe,
Ádám Dénes,
Dieter Edbauer,
Arthur Liesz
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20202411
Subject(s) - stroke (engine) , neuroinflammation , medicine , immunotherapy , clinical trial , pathophysiology , t cell , cell , neuroscience , immunology , immune system , inflammation , psychology , biology , mechanical engineering , engineering , genetics
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.