Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses

Nat Immunol. 2014 Apr;15(4):365-372. doi: 10.1038/ni.2842. Epub 2014 Mar 2.


T lymphocytes responding to microbial infection give rise to effector cells that mediate acute host defense and memory cells that provide long-lived immunity, but the fundamental question of when and how these cells arise remains unresolved. Here we combined single-cell gene-expression analyses with 'machine-learning' approaches to trace the transcriptional 'roadmap' of individual CD8(+) T lymphocytes throughout the course of an immune response in vivo. Gene-expression signatures predictive of eventual fates could be discerned as early as the first T lymphocyte division and may have been influenced by asymmetric partitioning of the receptor for interleukin 2 (IL-2Rα) during mitosis. Our findings emphasize the importance of single-cell analyses in understanding fate determination and provide new insights into the specification of divergent lymphocyte fates early during an immune response to microbial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity*
  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Computer Simulation
  • Gene Expression Profiling / methods*
  • Infections / immunology*
  • Infections / microbiology*
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitosis / genetics
  • Mitosis / immunology
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Single-Cell Analysis / methods*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / microbiology
  • T-Lymphocyte Subsets / virology
  • Transcriptional Activation / immunology


  • Receptors, Interleukin-2
  • Ovalbumin

Associated data

  • GEO/GSE54321