Regulation of Asymmetric Division by Atypical Protein Kinase C Influences Early Specification of CD8(+) T Lymphocyte Fates

Scientific Reports
Patrick J MetzJohn T Chang

Abstract

Naïve CD8(+) T lymphocytes responding to microbial pathogens give rise to effector T cells that provide acute defense and memory T cells that provide long-lived immunity. Upon activation, CD8(+) T lymphocytes can undergo asymmetric division, unequally distributing factors to the nascent daughter cells that influence their eventual fate towards the effector or memory lineages. Individual loss of either atypical protein kinase C (aPKC) isoform, PKCζ or PKCλ/ι, partially impairs asymmetric divisions and increases CD8(+) T lymphocyte differentiation toward a long-lived effector fate at the expense of memory T cell formation. Here, we show that deletion of both aPKC isoforms resulted in a deficit in asymmetric divisions, increasing the proportion of daughter cells that inherit high amounts of effector fate-associated molecules, IL-2Rα, T-bet, IFNγR, and interferon regulatory factor 4 (IRF4). However, unlike CD8(+) T cells deficient in only one aPKC isoform, complete loss of aPKC unexpectedly increased CD8(+) T cell differentiation toward a short-lived, terminal effector fate, as evidenced by increased rates of apoptosis and decreased expression of Eomes and Bcl2 early during the immune response. Together, these results provide evide...Continue Reading

References

May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·A T VellaP Marrack
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J M GraysonR Ahmed
Jun 3, 2000·Annual Review of Immunology·J T HartyD W White
Feb 13, 2001·Current Opinion in Cell Biology·C Q Doe, B Bowerman
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·A A LighvaniJ J O'Shea
Feb 26, 2003·Cell·Donald D Newmeyer, Shelagh Ferguson-Miller
May 20, 2003·Immunological Reviews·Douglas R Green
May 12, 2005·Current Opinion in Immunology·Antonio Lanzavecchia, Federica Sallusto
Nov 8, 2005·Nature Immunology·Andrew M IntlekoferSteven L Reiner
Jul 11, 2006·Immunological Reviews·Vladimir P Badovinac, John T Harty
Jul 25, 2006·Immunity·Jodie S HaringJohn T Harty
Oct 21, 2006·Nature Immunology·Matthew F Krummel, Ian Macara
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Naofumi TakemotoSteven L Reiner
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Timothy W HandSusan M Kaech
Nov 6, 2007·Developmental Cell·Bob Goldstein, Ian G Macara
Feb 26, 2008·Cell·Juergen A Knoblich
Aug 30, 2008·Journal of Clinical Immunology·Thomas R MalekAllison L Bayer
Dec 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Joshua J ObarLeo Lefrançois
Dec 9, 2009·Annual Review of Immunology·David R FooksmanMichael L Dustin
Jan 13, 2010·Immunity·Stephen C Jameson, David Masopust
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Yukiko M YamashitaAlan J Hunt
May 19, 2010·The Journal of Experimental Medicine·Carmen GerlachTon N M Schumacher
Jun 10, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jane OliaroSarah M Russell
Oct 6, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong Woo JungSusan M Kaech
Oct 12, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arnob BanerjeeSteven L Reiner
Oct 20, 2012·Nature Reviews. Immunology·Susan M Kaech, Weiguo Cui
Dec 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexis DunkleYou-Wen He
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Friederike RaczkowskiMagdalena Huber
May 20, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ribhu NayarLeslie J Berg
May 27, 2014·Nature Cell Biology·Yongliang Huo, Ian G Macara
Nov 15, 2014·Nature Immunology·John T ChangAnanda W Goldrath

❮ Previous
Next ❯

Citations

Sep 3, 2019·Cancer Cell·Miguel Reina-CamposJorge Moscat
Jun 22, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Teresa InfanteClaudio Napoli

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
Flow
Assay

Software Mentioned

- ASW Viewer
ImageJ
Treestar
FV10
FlowJo

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis