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Regulation of Asymmetric Division and CD8+ T Lymphocyte Fate Specification by PKCζ and PKCλ/ι

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.

During an immune response against a microbial pathogen, activated naïve 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. Here, we show that the absence of the atypical protein kinase C (aPKC) 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 aPKC in regulating asymmetric division and the specification of divergent CD8+ T lymphocyte fates early during an immune response.

Citation

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. "Regulation of Asymmetric Division and CD8+ T Lymphocyte Fate Specification by PKCζ and PKCλ/ι" Journal of Immunology (2015): 2,249–59