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

Heindl, S.; Ricci, A.; Carofiglio, O.; Zhou, Q.; Arzberger, T.; Lenart, N.; Franzmeier, N.; Hortobagyi, T.; Nelson, P. T.; Stowe, A. M.; Denes, A.; Edbauer, D. and Liesz, Arthur (26. May 2021): Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies. In: Journal of Experimental Medicine, Vol. 218, No. 8, e20202411

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.

• Item Type: Journal article
• EU Funded Grant Agreement Number: 802305
• EU Projects: Horizon 2020 > ERC Grants > ERC Starting Grant > ERC Grant 802305: RecoverInFlame - T cell-driven inflammatory mechanisms promote recovery after acute brain injury
• Form of publication: Publisher's Version
• Faculties: Medicine > Institute for Stroke and Dementia Research (ISD); Medicine > Munich Cluster for Systems Neurology (SyNergy)
• Subjects: 600 Technology > 610 Medicine and health
• Annotation: „This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).“ First published online
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198