CD8+ T lymphocyte expansion, proliferation and activation in dengue fever

PLoS Negl Trop Dis. 2015 Feb 12;9(2):e0003520. doi: 10.1371/journal.pntd.0003520. eCollection 2015 Feb.

Abstract

Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Brazil
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Dengue / immunology*
  • Dengue Virus / classification
  • Dengue Virus / immunology
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunologic Memory / immunology*
  • Ki-67 Antigen / metabolism
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocyte Count
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • HLA-DR Antigens
  • Ki-67 Antigen
  • Membrane Glycoproteins
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1

Grants and funding

The present work was supported by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazilian Ministry of Science and Technology (CNPq, grant #476088/2009-7 to EGK). AMM and EGK’s scholarships were supported by CNPq. KIC’s scholarship was supported by the Coordenação de Aperfeicoamento de Pessoal de Nível Superior, Brazilian Ministry of Education. URL of CNPq: URL www.cnpq.br; URL of CAPES: www.capes.gov.br. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.