Journal
NATURE IMMUNOLOGY
Volume 15, Issue 4, Pages 365-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ni.2842
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Funding
- US National Institutes of Health [DK080949, OD008469, AI095277, HG004659, NS075449]
- UCSD Digestive Diseases Research Development Center [DK80506]
- California Institute for Regenerative Medicine [RB1-01413, RB3-05009]
- National Science Foundation
- Alfred P. Sloan Foundation
- Howard Hughes Medical Institute
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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-2R alpha) 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.
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