Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies

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  • Steffanie Heindl
    Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 1
  • Alessio Ricci
    Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 1
  • Olga Carofiglio
    Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 1
  • Qihui Zhou
    German Center for Neurodegenerative Diseases, Munich, Germany 2
  • Thomas Arzberger
    Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 3
  • Nikolett Lenart
    Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary 5
  • Nicolai Franzmeier
    Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 1
  • Tibor Hortobagyi
    ELKH-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary 6
  • Peter T. Nelson
    University of Kentucky, Lexington, KY 7
  • Ann M. Stowe
    University of Kentucky, Lexington, KY 7
  • Adam Denes
    Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary 5
  • Dieter Edbauer
    German Center for Neurodegenerative Diseases, Munich, Germany 2
  • Arthur Liesz
    Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany 1

抄録

<jats:p>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.</jats:p>

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