Related Experiment Video

Updated: Feb 1, 2026

Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate
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Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate

Published on: September 13, 2019

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Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and

Jeff J Subleski1, Erika M Palmieri1, Jessica F Walls1,2

  • 1Cancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA.

Science Advances
|January 30, 2026
PubMed

Insights

Pyruvate kinase M2 (PKM2) is crucial for CD4 T cell survival. Its absence leads to increased PKM1, cell death, and reduced T cell-mediated colitis, highlighting PKM2

Area of Science:

  • Immunometabolism
  • Cellular metabolism
  • T cell biology

Background:

  • Glycolysis is vital for T cell expansion.
  • The specific roles of pyruvate kinase isoforms PKM1 and PKM2 in T cell metabolism are not fully understood.

Purpose of the Study:

  • To investigate the distinct functions of PKM1 and PKM2 in regulating CD4 T cell survival.
  • To determine the impact of PKM2 deficiency on T cell homeostasis and function.

Main Methods:

  • Utilized a pharmacological activator of PKM isoforms.
  • Employed targeted deletion of PKM2 in T cells.
  • Analyzed T cell populations in thymus and peripheral tissues.
  • Assessed T cell-mediated colitis models.

Main Results:

  • PKM2-deficient CD4 T cells showed increased PKM1 expression and mitochondrial reactive oxygen species-mediated cell death.
  • PKM2-deficient CD4 T cells were reduced in peripheral tissues with age but not in the thymus.
  • Absence of PKM2 led to less severe T cell-mediated colitis due to reduced pathogenic cells.

Conclusions:

  • PKM2 plays a critical role in CD4 T cell survival during both expansion and homeostasis.
  • PKM1 cannot fully compensate for PKM2's function in maintaining T cell survival.
  • Targeting PKM2 may offer therapeutic potential for inflammatory conditions like colitis.

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