CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke

  • J Cereb Blood Flow Metab. 2015 Jan;35(1):6-10. doi: 10.1038/jcbfm.2014.175.
Michael K Schuhmann  1 ,  Peter Kraft  2 ,  Guido Stoll  1 ,  Kristina Lorenz  3 ,  Sven G Meuth  4 ,  Heinz Wiendl  5 ,  Bernhard Nieswandt  6 ,  Tim Sparwasser  7 ,  Niklas Beyersdorf  8 ,  Thomas Kerkau  8 ,  Christoph Kleinschnitz  1
Affiliations
  • 1. Department of Neurology, University Clinics Würzburg, Würzburg, Germany.
  • 2. 1] Department of Neurology, University Clinics Würzburg, Würzburg, Germany [2] Institute of Clinical Epidemiology and Biometry, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
  • 3. Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
  • 4. 1] Department of Neurology, University of Münster, Münster, Germany [2] Institute of Physiology I-Neuropathophysiology, University of Münster, Münster, Germany.
  • 5. Department of Neurology, University of Münster, Münster, Germany.
  • 6. University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
  • 7. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • 8. Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
PMID: 25315859 DOI: 10.1038/jcbfm.2014.175
Abstract

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

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