high pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic t-cells during the course of secondary dengue virus infection高促炎细胞因子分泌高活动性和损失可交叉反应的细胞毒性t细胞过程中二次登革热病毒感染.pdfVIP

High Pro-Inflammatory Cytokine Secretion and Loss of High Avidity Cross-Reactive Cytotoxic T-Cells during the Course of Secondary Dengue Virus Infection 1. 1. 3 2 1 1 2 Tao Dong *, Edward Moran *, Nguyen Vinh Chau , Cameron Simmons , Kerstin Luhn , Yanchun Peng , Bridget Wills , Nguyen Phuong 2 3 3 1 2 1 Dung , Le Thi Thu Thao , Tran Tinh Hien , Andrew McMichael , Jeremy Farrar , Sarah Rowland-Jones 1 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom, 2 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam, 3 Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam Background. Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing – over half the world’s population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. Methods and Findings. Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue