TY - JOUR
T1 - Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis
AU - Klarquist, Jared
AU - Chitrakar, Alisha
AU - Pennock, Nathan D.
AU - Kilgore, Augustus M.
AU - Blain, Trevor
AU - Zheng, Connie
AU - Danhorn, Thomas
AU - Walton, Kendra
AU - Jiang, Li
AU - Sun, Jie
AU - Hunter, Christopher A.
AU - D’Alessandro, Angelo
AU - Kedl, Ross M.
N1 - Publisher Copyright:
Copyright © 2018 The Authors, some rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1126/sciimmunol.aas9822
DO - 10.1126/sciimmunol.aas9822
M3 - Article
C2 - 30194241
AN - SCOPUS:85054431810
SN - 2470-9468
VL - 3
JO - Science Immunology
JF - Science Immunology
IS - 27
M1 - eaas9822
ER -