Sirtuin 5 is Dispensable for CD8+ T Cell Effector and Memory Differentiation.

Qianqian Duan,Yong Liu,Yunan Zhao,Fangfang Li,Lianjun Zhang,Xiaowei Liu,Hongxiu Yu,Jiying Ding

doi:10.3389/fcell.2021.761193

Abstract

CD8+ T cell effector and memory differentiation is tightly controlled at multiple levels including transcriptional, metabolic, and epigenetic regulation. Sirtuin 5 (SIRT5) is a protein deacetylase mainly located at mitochondria, but it remains unclear whether SIRT5 plays key roles in regulating CD8+ T cell effector or memory formation. Herein, with adoptive transfer of Sirt5+/+ or Sirt5−/− OT-1 cells and acute Listeria monocytogenes infection model, we demonstrate that SIRT5 deficiency does not affect CD8+ T cell effector function and that SIRT5 is not required for CD8+ T cell memory formation. Moreover, the recall response of SIRT5 deficient memory CD8+ T cells is comparable with Sirt5+/+ memory CD8+ T cells. Together, these observations suggest that SIRT5 is dispensable for the effector function and memory differentiation of CD8+ T cells.

Highlights

CD8+ T cells are the main immune effector cells, protecting host against viral/bacterial infection and tumor development
T cell activation process is accompanied by striking metabolic switch from oxidative phosphorylation to aerobic glycolysis, and glycolytic metabolism is the key required for acquisition of CD8+ T cell effector functions (Chang et al, 2013)
We demonstrated that the mRNA expression of Sirtuin 5 (SIRT5) was decreased in purified antigen-specific memory CD8+ T cells after bacterial infection (Supplementary Figure S1A), indicating the potential roles of SIRT5 in regulating CD8+ T cell effector and memory differentiation

Summary

Introduction

CD8+ T cells are the main immune effector cells, protecting host against viral/bacterial infection and tumor development. Naïve CD8+ T cells undergo extensive proliferation and acquisition of effector functions, which is followed by memory T cell formation. The activation of naïve CD8+ T cells is marked with the upregulation of multiple surface markers including CD25, CD44, CD69, and CD98 and downregulation of CD62L. T cell activation process is accompanied by striking metabolic switch from oxidative phosphorylation to aerobic glycolysis, and glycolytic metabolism is the key required for acquisition of CD8+ T cell effector functions (Chang et al, 2013). Central memory CD8+ T cells (Tcm) display high level expression of CD62L, allowing their homing to lymph node (LN). Tcm cells exhibit substantial mitochondrial spare respiratory capacity (SRC) and fatty acid oxidation (FAO), which allows to sustain their long-term survival and metabolically prepared for secondary expansion (Zhang and Romero, 2018). Accumulating evidence suggests that T cell activation and differentiation are coupled to metabolic reprogramming, and alterations of metabolic activity can determine the CD8+ T cell fate (Zhang and Romero, 2018)

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Conclusion