Regulation of asymmetric division and CD8+ T lymphocyte fate specification by protein kinase Cζ and protein kinase Cλ/ι

Patrick J. Metz, Janilyn Arsenio, Boyko Kakaradov, Stephanie H. Kim, Kelly A. Remedios, Katherine Oakley, Kazunori Akimoto, Shigeo Ohno, Gene W. Yeo, John T. Chang

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21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2249-2259
Number of pages11
JournalJournal of Immunology
Volume194
Issue number5
DOIs
Publication statusPublished - 1 Mar 2015

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    Metz, P. J., Arsenio, J., Kakaradov, B., Kim, S. H., Remedios, K. A., Oakley, K., Akimoto, K., Ohno, S., Yeo, G. W., & Chang, J. T. (2015). Regulation of asymmetric division and CD8+ T lymphocyte fate specification by protein kinase Cζ and protein kinase Cλ/ι. Journal of Immunology, 194(5), 2249-2259. https://doi.org/10.4049/jimmunol.1401652