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Functional status of peripheral blood T-cells in ischemic stroke patients.

Vogelgesang A, May VE, Grunwald U, Bakkeboe M, Langner S, Wallaschofski H, Kessler C, Bröker BM, Dressel A - PLoS ONE (2010)

Bottom Line: 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.In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Greifswald, Greifswald, Germany.

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-alpha (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.

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Surviving T lymphocytes are functional.A) The proliferation expressed as stimulation index of T cells after ex vivo stimulation with PHA reveals normal proliferative responses of stroke patients (grey bars) lymphocytes compared to healthy controls (white bars) in the first week following stroke. Medians and interquartile ranges. n = 7; 36; 35; 32; (control; day 0; day 1; day 7). B–E) Ex vivo stimulation of T cells with PHA leads to increased proinflammatory cytokine release in supernatants of stroke patients cells (grey bars) compared to healthy controls (white bars) within the first week following stroke. * p<0.05; ** p<0.01. Medians and interquartile ranges. n(IL-1β, IL-6, TNFα, TNF-β) = 10; 37; 36; 28; (control; day 0; day 1; day 7).
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pone-0008718-g005: Surviving T lymphocytes are functional.A) The proliferation expressed as stimulation index of T cells after ex vivo stimulation with PHA reveals normal proliferative responses of stroke patients (grey bars) lymphocytes compared to healthy controls (white bars) in the first week following stroke. Medians and interquartile ranges. n = 7; 36; 35; 32; (control; day 0; day 1; day 7). B–E) Ex vivo stimulation of T cells with PHA leads to increased proinflammatory cytokine release in supernatants of stroke patients cells (grey bars) compared to healthy controls (white bars) within the first week following stroke. * p<0.05; ** p<0.01. Medians and interquartile ranges. n(IL-1β, IL-6, TNFα, TNF-β) = 10; 37; 36; 28; (control; day 0; day 1; day 7).

Mentions: To assess whether the surviving lymphocytes in stroke patients retained their functional capacity, ex vivo stimulation assays were performed. The proliferative capacity of the PBMC was unaltered during the first week following ischemic stroke (Fig. 5 A). The cells were stimulated with PHA and cytokine release was measured. This revealed a predominance of the proinflammatory cytokines IL-6, IL-1ß, TNF-α and TNF-β (Fig. 5 B–E) while IL-17, HMGB1 and IL-4, IL-5, IL-8, IL-10, IL-12p70 and IFN-γ remained unchanged (data not shown). Thus, the function of the surviving lymphocytes was intact and skewed towards proinflammation.


Functional status of peripheral blood T-cells in ischemic stroke patients.

Vogelgesang A, May VE, Grunwald U, Bakkeboe M, Langner S, Wallaschofski H, Kessler C, Bröker BM, Dressel A - PLoS ONE (2010)

Surviving T lymphocytes are functional.A) The proliferation expressed as stimulation index of T cells after ex vivo stimulation with PHA reveals normal proliferative responses of stroke patients (grey bars) lymphocytes compared to healthy controls (white bars) in the first week following stroke. Medians and interquartile ranges. n = 7; 36; 35; 32; (control; day 0; day 1; day 7). B–E) Ex vivo stimulation of T cells with PHA leads to increased proinflammatory cytokine release in supernatants of stroke patients cells (grey bars) compared to healthy controls (white bars) within the first week following stroke. * p<0.05; ** p<0.01. Medians and interquartile ranges. n(IL-1β, IL-6, TNFα, TNF-β) = 10; 37; 36; 28; (control; day 0; day 1; day 7).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2806837&req=5

pone-0008718-g005: Surviving T lymphocytes are functional.A) The proliferation expressed as stimulation index of T cells after ex vivo stimulation with PHA reveals normal proliferative responses of stroke patients (grey bars) lymphocytes compared to healthy controls (white bars) in the first week following stroke. Medians and interquartile ranges. n = 7; 36; 35; 32; (control; day 0; day 1; day 7). B–E) Ex vivo stimulation of T cells with PHA leads to increased proinflammatory cytokine release in supernatants of stroke patients cells (grey bars) compared to healthy controls (white bars) within the first week following stroke. * p<0.05; ** p<0.01. Medians and interquartile ranges. n(IL-1β, IL-6, TNFα, TNF-β) = 10; 37; 36; 28; (control; day 0; day 1; day 7).
Mentions: To assess whether the surviving lymphocytes in stroke patients retained their functional capacity, ex vivo stimulation assays were performed. The proliferative capacity of the PBMC was unaltered during the first week following ischemic stroke (Fig. 5 A). The cells were stimulated with PHA and cytokine release was measured. This revealed a predominance of the proinflammatory cytokines IL-6, IL-1ß, TNF-α and TNF-β (Fig. 5 B–E) while IL-17, HMGB1 and IL-4, IL-5, IL-8, IL-10, IL-12p70 and IFN-γ remained unchanged (data not shown). Thus, the function of the surviving lymphocytes was intact and skewed towards proinflammation.

Bottom Line: 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.In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Greifswald, Greifswald, Germany.

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-alpha (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.

Show MeSH
Related in: MedlinePlus