Dynamic Metabolic State of Tissue Resident CD8 T Cells.

Špela Konjar,Marc Veldhoen

doi:10.3389/fimmu.2019.01683

Abstract

In the past years, there have been significant advances in the understanding of how environmental conditions alone or in conjunction with pathogen invasion affect the metabolism of T cells, thereby influencing their activation, differentiation, and longevity. Detailed insights of the interlinked processes of activation and metabolism can contribute to major advances in immunotherapies. Naive and memory T cells circulate the body. In a quiescent state with low metabolic demands, they predominantly use oxidative phosphorylation for their energy needs. Recognition of cognate antigen combined with costimulatory signals results in a proliferative burst and effector molecule production, requiring rapid release of energy, achieved via dynamically reprogramming metabolic pathways. After activation, most T cells succumb to activation induced cell death, but few differentiate into memory T cells. Of note, some memory T cells permanently occupy tissues without circulating. These, tissue resident T cells are predominantly CD8 T cells, maintained in a metabolic state distinct from naïve and circulating memory CD8 T cells with elements similar to effector CD8 T cells but without undergoing proliferative burst or secreting immune mediators. They continually interact with tissue cells as part of an immune surveillance network, are well-adapted to the tissues they have made their home and where they may encounter different metabolic environments. In this review, we will discuss recent insights in metabolic characteristics of CD8 T cell biology, with emphasis on tissue resident CD8 T cells at the epithelial barriers.

Highlights

T lymphocytes, especially CD8-expresssing cytotoxic T cells, play a critical role in immune responses to intracellular microorganisms and cancer cells
In CD8 T cells, there are clear differences between the metabolic pathways used between naïve, memory and effector cells (Table 1)
CD8 TRM cells have characteristics of effector T cells, with increased expression of transcripts for proteins involved in metabolism and effector proteins such as granzymes, active cellular migration, as well as uptake of free fatty acids (FFA) and storage in lipid droplets, but without active proliferation or secretion of effector molecules such as IFN-γ

Summary

Introduction

T lymphocytes, especially CD8-expresssing cytotoxic T cells, play a critical role in immune responses to intracellular microorganisms and cancer cells. This suggests that the increased potential of memory T cells for OXPHOS is not explained by FAO, confirm recent results using carnitine palmitoyltransferase I (CPT1)-deficient cells, which cannot generate acetyl-CoA from long chain fatty acids [47].

Results

Conclusion