Acute hepatitis A (AHA) involves severe CD8 T cell-mediated liver injury. Here we showed during AHA, CD8 T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8 T cells. TCR-independent activation of non-HAV-specific CD8 T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8 T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8 T cells and the innate-like cytolytic activity of CD8 T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8 T cells, a result with implications for acute viral diseases.
Abstract-The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age-and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8 + T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8 + T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8 + T cells may offer new opportunities for the prevention and treatment of human hypertension. (Hypertension. 2013;62:126-133.)
Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8 1 CD57 1 T cells in acute MI patients. The frequency of CD57 1 cells among CD8 1 T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57 1 cells in the CD8 1 T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8 1 CD57 1 T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8 1 CD57 1 T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8 1 CD57 1 T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8 1 T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8 1 T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.
The 5.98 inch-sized World's first flexible OLED display has been developed and launched mass production on smartphone with extremely light, thin and curved shape, successfully. We have employed ELA-TFT on PI backplane, Face-sealing encapsulation, Laser-assisted glass release and flexible backplate lamination process. These technologies enable panel reliability as well as mass production with inherent flexible display characteristics. For commercializing flexible OLED, technical barriers and challenges on TFT device, panel design and various process technologies including LG Display's recent experience will be presented in this paper.
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