Longitudinal analysis of Memory B and T Cell responses to dengue virus in a 5-year prospective cohort study in Thailand

Luis A. Sánchez-Vargas, Sonia Kounlavouth, Madison L. Smith, Kathryn B. Anderson, Anon Srikiatkhachorn, Damon W. Ellison, Jeffrey R. Currier, Timothy P. Endy, Anuja Mathew, Alan L. Rothman

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2 Scopus citations

Abstract

Prior exposure to dengue virus (DENV) has a profound impact on the outcome of infection, which varies according to the interval between infections. Antibodies secreted by B cells and cytokines secreted by T cells are thought to contribute both to protective immunity against DENV and the pathogenesis of dengue disease. We analyzed peripheral blood mononuclear cells (PBMC) collected from Thai children over a 5-year prospective cohort study to define the dynamics of DENV-specific memory B and T cell responses and the impact of symptomatic or subclinical DENV infections. To measure B cell responses, PBMC were stimulated with IL-2 plus R848 and culture supernatants were tested for DENV-binding antibodies by ELISA. To measure T cell responses, PBMC were stimulated in dual-color ELISPOT assays with overlapping peptide pools of structural and non-structural proteins from the four DENV types. B cell responses were low to one or more DENV types prior to symptomatic infection and increased with reactivity to all four types after infection. Subjects who had a subclinical infection or who did not experience a DENV infection during the study period showed strong memory B cell responses to all four DENV types. T cell responses to DENV peptides demonstrated a cytokine hierarchy of IFN-γ > IL-2 > IFN-γ/IL-2. T cell responses were low or absent prior to secondary infections. The trends in T cell responses to DENV peptides over 3 year post-infection were highly variable, but subjects who had experienced a secondary DENV1 infection showed higher cytokine responses compared to subjects who had experienced a secondary DENV2 or subclinical infection. The longitudinal nature of our study demonstrates persistent memory B cell responses over years and a lasting but variable impact of secondary DENV infection on DENV-specific T cell responses.

Original languageEnglish (US)
Article number1359
JournalFrontiers in immunology
Volume10
Issue numberJUN
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
This work was supported by NIH grant P01AI034533 and the U.S. Military Infectious Diseases Research Program, and core facilities supported by NIH grant P20 GM104317.

Publisher Copyright:
© 2019 Sánchez-Vargas, Kounlavouth, Smith, Anderson, Srikiatkhachorn, Ellison, Currier, Endy, Mathew and Rothman.

Keywords

  • Antibodies
  • B cells
  • Cytokines
  • Dengue
  • ELISPOT
  • IFN-γ
  • IL-2
  • T cells

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