T-cell receptor signal strength and epigenetic control of Bim predict memory CD8+ T-cell fate

Kun Po Li, Brian H. Ladle, Sema Kurtulus, Allyson Sholl, Sharmila Shanmuganad, David A. Hildeman

Research output: Contribution to journalArticle

Abstract

Most effector CD8+ T cells die, while some persist and become either “effector” (TEM) or “central” (TCM) memory T cells. Paradoxically, effector CD8+ T cells with greater memory potential have higher levels of the pro-apoptotic molecule Bim. Here, we report, using a novel Bim-mCherry knock-in mouse, that cells with high levels of Bim preferentially develop into TCM cells. Bim levels remained stable and were regulated by DNA methylation at the Bim promoter. Notably, high levels of Bcl-2 were required for Bimhi cells to survive. Using Nur77-GFP mice as an indicator of TCR signal strength, Nur77 levels correlated with Bim expression and Nur77hi cells also selectively developed into TCM cells. Altogether, these data show that Bim levels and TCR signal strength are predictive of TEM- vs. TCM-cell fate. Further, given the many other biologic functions of Bim, these mice will have broad utility beyond CD8+ T-cell fate.

Original languageEnglish (US)
Pages (from-to)1214-1224
Number of pages11
JournalCell death and differentiation
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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