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.
Highlights
It has been observed for many years that immune cells transmigrate over the blood–brain barrier into infarcted brain tissue
This process follows a defined time course, with neutrophils and macrophages beginning to accumulate in the brain some hours after stroke, and lymphocytes reaching maximum infiltration by approximately day 3.1 While the detrimental role of nonregulatory T-cell subsets in the acute phase of ischemic stroke is widely accepted,[2,3,4] there is an ongoing debate about the contribution of regulatory T cells (Treg) to this pathology.[4,5,6,7]
The aim of this study was to clarify the impact of Treg in the acute phase of ischemic stroke by the means of a superagonistic anti-CD28 antibody (CD28 SA) that leads to an expansion of pre-existing Treg in the lymphoid organs and the dissemination of increased Treg numbers in the peripheral blood.[9,10]
Summary
It has been observed for many years that immune cells transmigrate over the blood–brain barrier into infarcted brain tissue This process follows a defined time course, with neutrophils and macrophages beginning to accumulate in the brain some hours after stroke, and lymphocytes reaching maximum infiltration by approximately day 3.1 While the detrimental role of nonregulatory T-cell subsets in the acute phase of ischemic stroke is widely accepted,[2,3,4] there is an ongoing debate about the contribution of regulatory T cells (Treg) to this pathology.[4,5,6,7]. We were able to show that Treg cause microvascular dysfunction and thrombus formation and secondary infarct growth in the acute phase after experimental ischemic stroke by interaction with endothelial cells and platelets.[4,8] This interplay between inflammatory processes and thrombus formation has recently been referred to as ‘thrombo-inflammation’.8. The aim of this study was to clarify the impact of Treg in the acute phase of ischemic stroke by the means of a superagonistic anti-CD28 antibody (CD28 SA) that leads to an expansion of pre-existing Treg in the lymphoid organs and the dissemination of increased Treg numbers in the peripheral blood.[9,10]
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