Regulatory CD8+CD122+ T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells

Sheetal Bodhankar, Yingxin Chen, Andrew Lapato, Arthur A. Vandenbark, Stephanie J. Murphy, Julie A. Saugstad, Halina Offner

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that transfer of IL-10+ B-cells reduced infarct volume in male C57BL/6J (wild-type, WT) recipient mice when given 24 h prior to or 4 h after middle cerebral artery occlusion (MCAO). The purpose of this study was to determine if passively transferred IL-10+ B-cells can exert therapeutic and immunoregulatory effects when injected 24 h after MCAO induction in B-cell-sufficient male WT mice. The results demonstrated that IL-10+ B-cell treated mice had significantly reduced infarct volumes in the ipsilateral cortex and hemisphere and improved neurological deficits vs. Vehicle-treated control mice after 60 min occlusion and 96 h of reperfusion. The MCAO-protected B-cell recipient mice had less splenic atrophy and reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres compared with Vehicle-treated control mice. These immunoregulatory changes occurred in concert with the predominant appearance of IL-10-secreting CD8+CD122+ Treg cells in both the spleen and the MCAO-affected brain hemisphere. This study for the first time demonstrates a major neuroprotective role for IL-10+ B-cells in treating MCAO in male WT mice at a time point well beyond the ~4 h tPA treatment window, leading to the generation of a dominant IL-10+CD8+CD122+ Treg population associated with spleen preservation and reduced CNS inflammation.

Original languageEnglish (US)
Article numberA003
Pages (from-to)911-924
Number of pages14
JournalMetabolic brain disease
Volume30
Issue number4
DOIs
StatePublished - Aug 1 2015

Keywords

  • IL-10-secreting B-cells
  • IL-10CD8CD122 regulatory T-cells
  • Inflammatory cells
  • MCAO

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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