title: Regulation of asymmetric division and CD8+ T lymphocyte fate specification by protein kinase Cζ and protein kinase Cλ/ι.
abstract: During an immune response against a microbial pathogen, activated naive T lymphocytes give rise to effector cells that provide acute host defense and memory cells that provide long-lived immunity. It has been shown that T lymphocytes can undergo asymmetric division, enabling the daughter cells to inherit unequal amounts of fate-determining proteins and thereby acquire distinct fates from their inception. In this study, we show that the absence of the atypical protein kinase C (PKC) isoforms, PKCζ and PKCλ/ι, disrupts asymmetric CD8(+) T lymphocyte division. These alterations were associated with aberrant acquisition of a pre-effector transcriptional program, detected by single-cell gene expression analyses, in lymphocytes that had undergone their first division in vivo and enhanced differentiation toward effector fates at the expense of memory fates. Together, these results demonstrate a role for atypical PKC in regulating asymmetric division and the specification of divergent CD8(+) T lymphocyte fates early during an immune response.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Metz
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Janilyn
authors.initials: J
authors.lastname: Arsenio
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell and Bioinformatics Programs, University of California San Diego, La Jolla, CA 92093; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Boyko
authors.initials: B
authors.lastname: Kakaradov
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Remedios
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors.forename: Katherine
authors.initials: K
authors.lastname: Oakley
authors.affiliation: Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa, Yokohama, Kanagawa Prefecture 236-0027, Japan;
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa, Yokohama, Kanagawa Prefecture 236-0027, Japan;
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell and Bioinformatics Programs, University of California San Diego, La Jolla, CA 92093; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093; Department of Physiology, National University of Singapore, Singapore 119077; and Molecular Engineering Laboratory and Genome Institute of Singapore, Agency for Science, Technology, and Research, Singapore 138632.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093; changj@ucsd.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007156:Immunologic Memory; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D059010:Single-Cell Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta