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Sterol regulatory element–binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity

Nature Immunology volume 14, pages 489499 (2013) | Download Citation


Newly activated CD8+ T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element–binding proteins (SREBPs) in the acquisition of effector-cell metabolism. Without SREBP signaling, CD8+ T cells were unable to blast, which resulted in attenuated clonal expansion during viral infection. Mechanistic studies indicated that SREBPs were essential for meeting the heightened lipid requirements of membrane synthesis during blastogenesis. SREBPs were dispensable for homeostatic proliferation, which indicated a context-specific requirement for SREBPs in effector responses. Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8+ T cells during the transition from quiescence to activation.

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We thank Y. Tone and M. Tone (Cedars-Sinai Medical Center) for retroviral vector MIGR1; T. Osborne (Sanford-Burnham Medical Research Institute) for polyclonal antibody to SREBP1 or SREBP2; A. Do, L. Pang, A. Armijo and C. Radu for technical assistance; and P. Tontonoz and M. Day for critical feedback on the manuscript. Supported by the US National Institutes of Health (AI093768 to S.J.B., and AI082975 and AI085043 to D.G.B.), the Jonsson Comprehensive Cancer Center Foundation of the University of California, Los Angeles (S.J.B. and Y.K.), the National Center for Research Resources (S10RR026744 to L.V. and K.R.), the National Cancer Institute of the US National Institutes of Health (T32-CA009120-36 to K.J.W.), the US Public Health Service (T32-GM008469 to J.P.A.) and the University of California, Los Angeles, Graduate Division (J.P.A.).

Author information

Author notes

    • M Benjamin Hock

    Present address: Amgen, Thousand Oaks, California, USA.


  1. Institute for Molecular Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Yoko Kidani
    • , M Benjamin Hock
    • , Kevin J Williams
    • , Joseph P Argus
    • , Beth N Marbois
    • , Thomas G Graeber
    •  & Steven J Bensinger
  2. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Yoko Kidani
    • , M Benjamin Hock
    • , Kevin J Williams
    •  & Steven J Bensinger
  3. Department of Microbiology, Immunology, & Molecular Genetics, and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Heidi Elsaesser
    • , Elizabeth B Wilson
    •  & David G Brooks
  4. Department of Human Genetics, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, California, USA.

    • Laurent Vergnes
    •  & Karen Reue
  5. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Joseph P Argus
    • , Evangelia Komisopoulou
    • , Thomas G Graeber
    •  & Steven J Bensinger
  6. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.

    • Beth N Marbois
  7. Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Evangelia Komisopoulou
    •  & Thomas G Graeber
  8. Metabolic Signaling and Disease Program, Diabetes and Obesity Center, Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.

    • Timothy F Osborne
  9. Department of Medicine, David Geffen School of Medicine, and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.

    • Karen Reue


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Y.K. designed, did and analyzed most of the experiments and wrote the manuscript; H.E., M.B.H., L.V., K.J.W., J.P.A., B.N.M., E.K. and E.B.W. did experiments and analyzed data; T.F.O. provided materials and intellectual input; and S.J.B. provided overall coordination for the conception, design and supervision of the study and wrote the manuscript (with input from T.F.O., T.G.G., K.R. and D.G.B.).

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Steven J Bensinger.

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