Early effector maturation of naïve human CD8+ Tcells requires mitochondrial biogenesis.

Abstract

The role of mitochondrial biogenesis during naïve 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 naïve CD8+ Tcells. Specifically, we found that prior to the first round of cell division activated naïve 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-γ, perforin, and granzyme B production. Together, these findings point to the importance of mitochondrial biogenesis during early effector maturation of CD8+ Tcells.