title: Regulatory CD8(+)CD122 (+) T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells.
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.
authors.affiliation: Neuroimmunology Research, VA Medical Center, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bodhankar
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Neuroimmunology Research, VA Medical Center, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lapato
authors.affiliation: Neuroimmunology Research, VA Medical Center, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.|Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Saugstad
authors.affiliation: Neuroimmunology Research, VA Medical Center, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.|Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000008:administration & dosage / Q000378:metabolism*; D053646:Interleukin-2 Receptor beta Subunit / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: C556062:IL10 protein, mouse; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D016753:Interleukin-10