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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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CD4+ T-cells in the peripheral blood of stroke patients are activated.Comparison of expression of activation markers on lymphocytes between healthy controls (white bars) and stroke patients (grey bars) in the first two weeks following stroke reveal that CD4+ T-cells in the peripheral blood are activated. * p<0.05; ** p<0.01; *** p<0.001. Medians and interquartile ranges. n(CD4+CD25+, CD25+%CD4+) = 14; 33; 32; 24; 14; n(CD4+HLA-DR+) = 12; 64; 66; 42; 22; n(HLA-DR+%CD4+) = 12; 63; 66; 43; 22; (control; day 0; day 1; day 7; day14).
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pone-0008718-g003: CD4+ T-cells in the peripheral blood of stroke patients are activated.Comparison of expression of activation markers on lymphocytes between healthy controls (white bars) and stroke patients (grey bars) in the first two weeks following stroke reveal that CD4+ T-cells in the peripheral blood are activated. * p<0.05; ** p<0.01; *** p<0.001. Medians and interquartile ranges. n(CD4+CD25+, CD25+%CD4+) = 14; 33; 32; 24; 14; n(CD4+HLA-DR+) = 12; 64; 66; 42; 22; n(HLA-DR+%CD4+) = 12; 63; 66; 43; 22; (control; day 0; day 1; day 7; day14).

Mentions: It is well documented that following stroke a large fraction of T cells is rapidly lost from the peripheral blood. To determine the activation status of the remaining T cells the expression of the established T cell activation markers IL-2 receptor (CD25) and HLA-DR were measured. Compared to controls, an increased proportion of CD4+ T-cells expressed CD25 (p = 0.02) or HLA-DR (p<0.0001), respectively (Fig. 3). This corresponded to a net increase in CD4+ HLA-DR+ T-cell numbers (p = 0.0055) despite the reduction of the total numbers of CD4+ T-cells. A similar trend was observed for CD4+CD25+ T-cells. This shows that in stroke CD4+ T-cells in the peripheral blood become activated.


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)

CD4+ T-cells in the peripheral blood of stroke patients are activated.Comparison of expression of activation markers on lymphocytes between healthy controls (white bars) and stroke patients (grey bars) in the first two weeks following stroke reveal that CD4+ T-cells in the peripheral blood are activated. * p<0.05; ** p<0.01; *** p<0.001. Medians and interquartile ranges. n(CD4+CD25+, CD25+%CD4+) = 14; 33; 32; 24; 14; n(CD4+HLA-DR+) = 12; 64; 66; 42; 22; n(HLA-DR+%CD4+) = 12; 63; 66; 43; 22; (control; day 0; day 1; day 7; day14).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0008718-g003: CD4+ T-cells in the peripheral blood of stroke patients are activated.Comparison of expression of activation markers on lymphocytes between healthy controls (white bars) and stroke patients (grey bars) in the first two weeks following stroke reveal that CD4+ T-cells in the peripheral blood are activated. * p<0.05; ** p<0.01; *** p<0.001. Medians and interquartile ranges. n(CD4+CD25+, CD25+%CD4+) = 14; 33; 32; 24; 14; n(CD4+HLA-DR+) = 12; 64; 66; 42; 22; n(HLA-DR+%CD4+) = 12; 63; 66; 43; 22; (control; day 0; day 1; day 7; day14).
Mentions: It is well documented that following stroke a large fraction of T cells is rapidly lost from the peripheral blood. To determine the activation status of the remaining T cells the expression of the established T cell activation markers IL-2 receptor (CD25) and HLA-DR were measured. Compared to controls, an increased proportion of CD4+ T-cells expressed CD25 (p = 0.02) or HLA-DR (p<0.0001), respectively (Fig. 3). This corresponded to a net increase in CD4+ HLA-DR+ T-cell numbers (p = 0.0055) despite the reduction of the total numbers of CD4+ T-cells. A similar trend was observed for CD4+CD25+ T-cells. This shows that in stroke CD4+ T-cells in the peripheral blood become activated.

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