title: Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Janilyn
authors.initials: J
authors.lastname: Arsenio
authors.affiliation: Department of Cellular and Molecular Medicine, UCSD Stem Cell and Bioinformatics Programs, and Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Boyko
authors.initials: B
authors.lastname: Kakaradov
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Metz
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Cellular and Molecular Medicine, UCSD Stem Cell and Bioinformatics Programs, and Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.|Department of Physiology, National University of Singapore and Genome Institute of Singapore and Molecular Engineering Laboratory, ASTAR, Singapore.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D007239:Infections / Q000276:immunology* / Q000382:microbiology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D059010:Single-Cell Analysis / Q000379:methods*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D015375:Receptors, Interleukin-2; D010047:Ovalbumin