Cell
Volume 174, Issue 1, 28 June 2018, Pages 117-130.e14
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Article
Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection

https://doi.org/10.1016/j.cell.2018.05.029Get rights and content
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Highlights

  • Fate mapping reveals developmental layers in the CD8+ T cell response to infection

  • The fetal layer of CD8+ T cells exhibits rapid and innate-like functions in adults

  • The adult layer of CD8+ T cells preferentially gives rise to long-lived memory cells

  • CD8+ T cells with different developmental origins possess distinct regulomes

Summary

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
immune ontogeny
development
neonate
homeostatic proliferation
post-thymic maturation
epigenetics
virtual memory cells
effector cell differentiation
immunological memory

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