Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 48, Issue 10, Pages 1632-1643Publisher
WILEY
DOI: 10.1002/eji.201747443
Keywords
CD8(+) Tcells; Immunometabolism; Metabolism; Mitochondrial biogenesis; ROS
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Funding
- Swiss National Science Foundation [31003A_135677/1, 31003A_172848, CRSII3_160, 323530_139181, 323530_158119]
- Basel University Excellent Young Researcher Grants
- Swiss National Science Foundation (SNF) [31003A_135677, 323530_158119, 31003A_172848, 323530-139181] Funding Source: Swiss National Science Foundation (SNF)
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The role of mitochondrial biogenesis during naive to effector differentiation of CD8(+) Tcells remains ill explored. In this study, we describe a critical role for early mitochondrial biogenesis in supporting cytokine production of nascent activated human naive CD8(+) Tcells. Specifically, we found that prior to the first round of cell division activated naive CD8(+) Tcells rapidly increase mitochondrial mass, mitochondrial respiration, and mitochondrial reactive oxygen species (mROS) generation, which were all inter-linked and important for CD8(+) Tcell effector maturation. Inhibition of early mitochondrial biogenesis diminished mROS dependent IL-2 production - as well as subsequent IL-2 dependent TNF, IFN-, perforin, and granzyme B production. Together, these findings point to the importance of mitochondrial biogenesis during early effector maturation of CD8(+) Tcells.
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