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Cell. 2018 Jun 28;174(1):117-130.e14. doi: 10.1016/j.cell.2018.05.029. Epub 2018 Jun 14.

Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection.

Author information

1
Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
3
Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, NSW 2052, Australia.
4
RNA Sequencing Core, Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
5
Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA. Electronic address: bdr54@cornell.edu.

Abstract

Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8+ T cell pool that are distinguished by their developmental origin, unique transcriptional profiles, distinct chromatin landscapes, and different kinetics and phenotypes after microbial challenge. These data demonstrate that the naive CD8+ T cell pool is not as homogeneous as previously thought and offers a new framework for explaining the remarkable heterogeneity in the effector and memory T cell subsets that arise after infection.

KEYWORDS:

CD8(+) T cell; development; effector cell differentiation; epigenetics; homeostatic proliferation; immune ontogeny; immunological memory; neonate; post-thymic maturation; virtual memory cells

PMID:
29909981
DOI:
10.1016/j.cell.2018.05.029
[Indexed for MEDLINE]

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