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Clin Immunol. 2019 Apr 4;203:14-22. doi: 10.1016/j.clim.2019.04.002. [Epub ahead of print]

Characteristics of regulatory T-cell populations before and after Ty21a typhoid vaccination in children and adults.

Author information

1
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Molecular Microbiology and Immunology Department, University of Maryland Graduate Program in Life Sciences, Baltimore, MD, USA. Electronic address: mark.rudolph@umaryland.edu.
2
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
4
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
5
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
6
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Molecular Microbiology and Immunology Department, University of Maryland Graduate Program in Life Sciences, Baltimore, MD, USA; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: msztein@som.umaryland.edu.

Abstract

Typhoid fever, caused by the pathogen Salmonella enterica serovar Typhi (S. Typhi), is a serious global health concern. Challenge studies with wild type S. Typhi identified associations between gut-homing regulatory T cells (Treg) and development of typhoid disease. Whether oral live-attenuated Ty21a vaccination induces gut-homing Treg remains unclear. Here, we analyze pediatric and adult Treg pre- and post-Ty21a vaccination in an autologous S. Typhi-antigen presentation model to address this knowledge gap. We show that peripheral memory Treg populations change from childhood to adulthood, but not following Ty21a vaccination. Unsupervised dimensionality reduction with t-distributed stochastic neighbor embedding (tSNE) identifies homing, memory, and functional features which evidence age-associated maturation of multifunctional S. Typhi-responsive Treg, which were not impacted by Ty21a vaccination. These findings improve understanding of pediatric regulatory T cells, while identifying age-related differences in S. Typhi-responsive Treg, which may aid in the development of improved pediatric vaccination strategies against S. Typhi.

KEYWORDS:

Dimensionality reduction; Pediatric immunology; Regulatory T cells; Salmonella Typhi; Ty21a; Typhoid

PMID:
30953793
DOI:
10.1016/j.clim.2019.04.002

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