title: Lower activation-induced T-cell apoptosis is related to the pathological immune response in secondary infection with hetero-serotype dengue virus.
abstract: The available evidence suggests that dengue virus-specific T lymphocytes and cytokine storm play a pivotal role in the immunopathogenesis of plasma leakage. Investigations are underway to identify the immune profiles associated with increased or decreased risk for severe disease. In this study, CD14+ cells from the peripheral blood mononuclear cells (PBMCs) of patients who recovered from DENV-1 infection were infected with DENV-1 or DENV-2 and co-cultured with memory T cells. We found that secondary infection with DENV-2 suppresses the cell reproductive capacity but forms more cell clones and more functional cells to produce more proinflammatory factors (IFN-γ, TNF-α, IL-6, IL-8, IL-12 and IL-17) and less regulatory cytokines (IL-10, TGF-β) which results in higher viral replication compared to secondary infection with DENV-1. Memory dengue virus-specific T cells which are induced in a primary dengue virus infection are reactivated by the heterologous serotype of dengue virus and antigen-presenting cells (APCs) during a secondary infection. Dramatically, less apoptosis and more continuous activation of T cells in secondary infection with hetero-serotype DENV were observed. This discovery which has not been reported previously may be the reasonable and vital interpretation for the cytokine storm and severe symptoms observed in secondary infection with DENV. In summary, secondary infection with hetero-serotype DENV elicits the relatively pathological immune response while secondary infection with homologous-serotype DENV induces the relatively protective immune response by activation-induced cell death (AICD) of T cells.
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yang
authors.affiliation: Guangzhou Military Command Center for Disease Control and Prevention, PLA, Guangzhou 510507, China.
authors.forename: Huacheng
authors.initials: H
authors.lastname: Yan
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Yu
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Guangzhou Military Command Center for Disease Control and Prevention, PLA, Guangzhou 510507, China. Electronic address: renruiwen@hotmail.com.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Ren
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China. Electronic address: ljtqms@qq.com.
authors.forename: Jintao
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D060085:Coinfection; D016207:Cytokines / Q000378:metabolism; D003715:Dengue / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000145:classification* / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D065288:Serogroup; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Apoptosis; Dengue virus; Hetero-serotype; Secondary infection; T cell