Longitudinal Analysis of Memory B and T Cell Responses to Dengue Virus in a 5-Year Prospective Cohort Study in Thailand.

Autor:	Sánchez-Vargas LA; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States., Kounlavouth S; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States., Smith ML; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States., Anderson KB; Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States., Srikiatkhachorn A; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States., Ellison DW; Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand., Currier JR; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States., Endy TP; Department of Microbiology and Immunology, State University of New York-Upstate Medical University, Syracuse, NY, United States., Mathew A; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States., Rothman AL; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Jun 13; Vol. 10, pp. 1359. Date of Electronic Publication: 2019 Jun 13 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.01359
Abstrakt:	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.
Databáze:	MEDLINE
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