title: Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue.
abstract: Dengue fever, a public health problem in Brazil, may present severe clinical manifestations as result of an increased vascular permeability and coagulation disorders. T cell activation is a critical event for an effective immune response against infection, including the production of cytokines. We aim to reveal mechanisms that modulate the virus-cell interaction, with an emphasis on cell death. Apoptosis is involved in lymphocyte homeostasis, contributes to the clearance of virus-infected cells but also may play a role in the pathogenesis. Phosphatidylserine exposure on CD8T lymphocytes from dengue patients support early apoptotic processes and loss of genomic integrity, observed by DNA fragmentation in T lymphocytes and indicating late apoptosis. These T cells express activation and cytotoxic phenotypes as revealed by CD29 and CD107a upregulation. Higher frequencies of CD95 were detected in T lymphocytes mainly in those with the cytotoxic profile (CD107a+) and lower levels of anti-apoptotic molecule Bcl-2, suggesting that both CD4+ and CD8+ T cell subsets are more susceptible to apoptosis during acute dengue. The analysis of apoptosis-related protein expression profile showed that not only molecules with pro- but also those with anti-apoptotic functions are overexpressed, indicating that survival mechanisms could be possibly protecting cells against apoptosis caused by viral, immune, oxidative and/or genotoxic stresses. These observations led us to propose that in dengue patients there is an association between T cell susceptibility to apoptosis and the activation state. The mechanisms for understanding the immunopathogenesis during dengue infection are discussed.
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil. Electronic address: torrentes@ioc.fiocruz.br.
authors: Amanda
authors: A
authors: Torrentes-Carvalho
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil.
authors: Cintia Ferreira
authors: CF
authors: Marinho
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil.
authors: Luzia Maria
authors: LM
authors: de Oliveira-Pinto
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil.
authors: Débora Batista
authors: DB
authors: de Oliveira
authors: Hospital Universitário Pedro Ernesto, UERJ and Hospital Universitário Gafreé-Guinle, UNIRIO, RJ, Brazil.
authors: Paulo Vieira
authors: PV
authors: Damasco
authors: Departamento de Clínica Médica, FM, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil.
authors: Rivaldo Venâncio
authors: RV
authors: Cunha
authors: Centro de Referência em Dengue e Faculdade de Medicina, Campos de Goytacazes, RJ, Brazil.
authors: Luiz José
authors: LJ
authors: de Souza
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil.
authors: Elzinandes Leal
authors: EL
authors: de Azeredo
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil. Electronic address: claire@ioc.fiocruz.br.
authors: Claire Fernandes
authors: CF
authors: Kubelka
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015415:Biomarkers; D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic; D053938:DNA Fragmentation; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D051997:ADP-ribosyl Cyclase 1
keywords: Activation markers; Apoptosis; Dengue; Lymphocytes