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

Steffanie Heindl, Alessio Ricci, Olga Carofiglio, Qihui Zhou, Thomas Arzberger, Nikolett Lenart, Nicolai Franzmeier, Tibor Hortobagyi, Peter T. Nelson, Ann M. Stowe, Adam Denes, Dieter Edbauer, Arthur Liesz

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Article numbere20202411
JournalJournal of Experimental Medicine
Volume218
Issue number8
DOIs
StatePublished - May 26 2021

Bibliographical note

Funding Information:
We would like to thank Kerstin Thuβ-Silczak and Christina Fürle for technical support as well as Juliet Stowe for the selection and preparation of human tissue samples from the Sanders Brown Center on Aging (supported by National Institutes of Health grant P30 AG028383).

Funding Information:
This work was funded by the European Research Council (grant ERC-StGs 802305 to A. Liesz and grant ERC-PoC 875677 to D. Ed-bauer), the American Heart Association (grant 19EIA34760279 to A.M. Stowe), the Hungarian Brain Research Program (grant 2017-1.2.1-NKP-2017-00002), and the German Research Foundation under Germany’s Excellence Strategy (EXC 2145 SyNergy, ID 390857198) through the collaborative research center TRR274 (project ID 408885537) and under grants LI-2534/6-1 and LI-2534/7-1. D. Edbauer received funding from the NOMIS Foundation.

Publisher Copyright:
© 2021 Heindl et al.

ASJC Scopus subject areas

  • Medicine (all)

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