Dataset Information

High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells.

ABSTRACT: Cellular and humoral constituents of the immune system differ significantly between children and adults, yet very little is known about the impact of early-life pathogen exposure on this immunologic transition. We examined CD4+ and CD8+ T cell subsets defined by CCR7 and CD45RA expression in two longitudinal pediatric cohorts experiencing divergent levels of pathogen burden. Using multiparameter flow cytometry, along with serological, cytokine, and transcriptomic data, we show that cumulative pathogen burden promotes the development of atypical CD8dim T cells with an innate-like profile (Granzyme Bhi, IFN?low, TNF?low, PLFZhi, ID2hi, IKZF2hi) in contrast to age-matched children residing in a low pathogen-exposure area who display a more conventional CD8bright profile (IFN?+, TNF?+, CCL4+). Furthermore, these unconventional T cells had stunted proliferation, distinct transcriptional programs, and impaired T cell receptor signaling and were enriched in hallmark TNF?, NF-?B, and IL-6 gene signaling pathways, reminiscent of NK cells and type-1 innate lymphoid cells. Our findings suggest that these unconventional CD8dim T cells arise in a very particular immunological context and may provide a deeper understanding of the heterogeneity in human immune responses.

SUBMITTER: Falanga YT

PROVIDER: S-EPMC5543908 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells.

Falanga Yves T YT Frascoli Michela M Kaymaz Yasin Y Forconi Catherine C Ong'echa John Michael JM Bailey Jeffrey A JA Berg Leslie J LJ Moormann Ann M AM

JCI insight 20170803 15

Cellular and humoral constituents of the immune system differ significantly between children and adults, yet very little is known about the impact of early-life pathogen exposure on this immunologic transition. We examined CD4+ and CD8+ T cell subsets defined by CCR7 and CD45RA expression in two longitudinal pediatric cohorts experiencing divergent levels of pathogen burden. Using multiparameter flow cytometry, along with serological, cytokine, and transcriptomic data, we show that cumulative pa ...[more]

PMID: 28768916

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Dataset Information

High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells.

Publications

High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells.

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