Mouse lung tissue resident memory CD8 T cells exhibit unique metabolic profiles

Abstract

Abstract Tissue resident memory T cells (TRM) confer protection against a variety of illnesses ranging from infections to cancers. As demonstrated in the skin, transfer of TRM from immune to naïve hosts is sufficient to prevent herpes simplex virus type 1 (HSV) associated pathology. Comparably, the presence of antigen-specific TRM in a mouse model of melanoma can limit tumor growth. In the lungs, TRM offer critical for protection against influenza, even in the absence of specific antibodies. In the skin, the functions of different CD8 T cell subsets have been linked with distinct metabolic pathways. Skin TRM display a unique metabolic profile to other CD8 memory cells subsets. They undergo enhanced fatty acid oxidation and oxidative phosphorylation as compared with circulating memory cells and naïve cells. However, it is unclear if this programming is universal between all TRM subsets and holds true in the lung. We hypothesize that lung TRM with different integrin profiles will utilize unique metabolic programs. Metabolic profiles of lung CD8 T cells were assessed using a variety of functional metabolic assays including glucose analogue uptake, fatty acid uptake, and oxidative phosphorylation as assessed by fluorescent dyes measured by flow cytometry. Nonfunctional assays including neutral lipid storage, mitochondrial mass, and mRNA transcript levels of key metabolic genes were also assessed via flow cytometry using fluorescent dyes, while transcripts were quantified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Our findings indicate that lung TRM show enhanced fatty acid oxidation, more neutral lipid storage, and less glucose uptake than their non-TRM T cells in our influenza mouse model.