Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis

Jared Klarquist, Alisha Chitrakar, Nathan D. Pennock, Augustus M. Kilgore, Trevor Blain, Connie Zheng, Thomas Danhorn, Kendra Walton, Li Jiang, Jie Sun, Christopher A. Hunter, Angelo D’Alessandro, Ross M. Kedl

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


In contrast to responses against infectious challenge, T cell responses induced via adjuvanted subunit vaccination are dependent on interleukin-27 (IL-27). We show that subunit vaccine–elicited cellular responses are also dependent on IL-15, again in contrast to the infectious response. Early expression of interferon regulatory factor 4 (IRF4) was compromised in either IL-27– or IL-15–deficient environments after vaccination but not infection. Because IRF4 facilitates metabolic support of proliferating cells via aerobic glycolysis, we expected this form of metabolic activity to be reduced in the absence of IL-27 or IL-15 signaling after vaccination. Instead, metabolic flux analysis indicated that vaccine-elicited T cells used only mitochondrial function to support their clonal expansion. Loss of IL-27 or IL-15 signaling during vaccination resulted in a reduction in mitochondrial function, with no corresponding increase in aerobic glycolysis. Consistent with these observations, the T cell response to vaccination was unaffected by in vivo treatment with the glycolytic inhibitor 2-deoxyglucose, whereas the response to viral challenge was markedly lowered. Collectively, our data identify IL-27 and IL-15 as critical to vaccine-elicited T cell responses because of their capacity to fuel clonal expansion through a mitochondrial metabolic program previously thought only capable of supporting quiescent naïve and memory T cells.

Original languageEnglish (US)
Article numbereaas9822
JournalScience Immunology
Issue number27
StatePublished - 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis'. Together they form a unique fingerprint.

Cite this