Uncoupling protein 2 regulates metabolic reprogramming and fate of antigen-stimulated CD8+ T cells

Leena Chaudhuri, Rupesh K. Srivastava, Ferdynand Kos, Protul A. Shrikant

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Adoptive cell therapy (ACT) employing ex vivo-generated tumor antigen-specific CD8+ T cells shows tumor efficacy when the transferred cells possess both effector and memory functions. New strategies based on understanding of mechanisms that balance CD8+ T cell differentiation toward effector and memory responses are highly desirable. Emerging information confirms a central role for antigen-induced metabolic reprogramming in CD8+ T cell differentiation and clonal expansion. The mitochondrial protein uncoupling protein 2 (UCP2) is induced by antigen stimulation of CD8+ T cells; however, its role in metabolic reprogramming underlying differentiation and clonal expansion has not been reported. Employing genetic (siRNA) and pharmacologic (Genipin) approaches, we note that antigen-induced UCP2 expression reduces glycolysis, fatty acid synthesis and production of reactive oxygen species to balance differentiation with survival of effector CD8+ T cells. Inhibition of UCP2 promotes CD8+ T cell terminal differentiation into short-lived effector cells (CD62LloKLRG1HiIFNγHi) that undergo clonal contraction. These findings are the first to reveal a role for antigen-induced UCP2 expression in balancing CD8+ T cell differentiation and survival. Targeting UCP2 to regulate metabolic reprogramming of CD8+ T cells is an attractive new approach to augment efficacy of tumor therapy by ACT.

Original languageEnglish (US)
Pages (from-to)869-874
Number of pages6
JournalCancer Immunology, Immunotherapy
Issue number7
StatePublished - Jul 1 2016


  • CD8+ T cell fate
  • CITIM 2015
  • Metabolic reprogramming
  • Uncoupling protein 2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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