Abstract
Stroke is a major cause of disability and leading cause of death in the northern hemisphere. Only recently it became evident that cerebral ischemia not only leads to brain tissue damage and subsequent local inflammation but also to a dramatic loss of peripheral blood T-cells with subsequent infections. However, only scarce information is available on the activation status of surviving T cells. This study therefore addressed the functional consequences of immunological changes induced by stroke in humans. For this purpose peripheral blood T-cells were isolated from 93 stroke patients and the expression of activation makers was determined. In addition ex vivo stimulation assays were applied to asses the functionality of T cells derived from blood of stroke patients. Compared to healthy controls, stroke patients demonstrated an enhanced surface expression of HLA-DR (p<0.0001) and CD25 (p = 0.02) on T cells, revealing that stroke leads to T cell activation, while CTLA-4 remained undetectable. In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells. Ex vivo, T cells of stroke patients proliferated unimpaired and released increased amounts of the proinflammatory cytokine TNF-α (p<0.01) and IL-6 (p<0.05). Also, in sera of stroke patients HMGB1 concentrations were increased (p = 0.0002). The data demonstrate that surviving T cells in stroke patients remain fully functional and are primed towards a TH1 response, in addition we provide evidence that catecholamine mediated inhibition of CTLA-4 expression and serum HMGB1 release are possible mediators in stroke induced activation of T cells.
Highlights
Stroke is a major cause of disability and leading cause of death in the northern hemisphere, second only to cardiac disease, and is accompanied by a grave economic impact [1]
Of special interest were the kinetics of serum cytokine concentrations and differences in T cell function between stroke patients with subsequent infection and those, who remained free from this complication
Previous studies have addressed the changes in serum cytokines and cellularity following ischemic stroke in humans [5,6,7,17,18,19]
Summary
Stroke is a major cause of disability and leading cause of death in the northern hemisphere, second only to cardiac disease, and is accompanied by a grave economic impact [1]. Serum HMGB1 strongly promotes inflammation, regulates dendritic cell function and migration, skews the T cell response towards a Th1 profile and induces proliferation and the release of IL-6 [11,12,13] HMGB1, which has been shown to be elevated within 24 hours following stroke or myocardial infarction, could act as important player in the modulation of post stroke immune responses. This molecule has been shown to contribute to brain tissue destruction following brain injury [13,14,15]. Of special interest were the kinetics of serum cytokine concentrations and differences in T cell function between stroke patients with subsequent infection and those, who remained free from this complication
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