Phenotypic and Clonal Stability of Antigen-Inexperienced Memory-like T Cells across the Genetic Background, Hygienic Status, and Aging

Abstract

The animal facility of the IMG is a part of the Czech Centre for Phenogenomics and the work there was supported in part by following grants: LM2015040, LM2018126, OP RDI CZ.1.05/2.1.00/19.0395, OP RDI BIOCEV CZ.1.05/1.1.00/02.0109 provided by the Czech Ministry of Education, Youth and Sports and the European Regional Development Fund. AM performed most of the experiments. VN, LS, MP, AD, RS, TM, AN, KK, PS, OS performed experiments. AM, VN, and OS analyzed data and finalized figures. JKu and JM analyzed the transcriptomic data. JN analyzed the TCR profiling data. DC and JKr analyzed the S16 sequencing data. RS and PS provided feral mice. TH and HK provided germ-free mice. MK, HK, JKr, PS, and OS supervised the work. OS conceived the study.

Signals for antigen-independent differentiation of memory CD8+ T cells

“…Whether T IM and T VM are different stages of one T AIM subset or different subsets is still the topic of ongoing discussion [4,16,36]. It has recently been proposed that CD122 expression can function as marker to distinguish T IM and T VM in the periphery, with T IM cells having lower expression of CD122 than T VM but higher than T N [11]. A detailed overview of T AIM surface markers is provided in Table 1.…”

“…A role for TCR quality was further supported by a study using mice with a transgenic TCRα and TCRβ chain. When these tgTCR mice are bred on a Rag-KO background, recombination of endogenous TCR genes is prevented and all T cells express the exact same TCR [11].…”

“…The number of T AIM cells is also regulated during normal physiological development and it changes during life. Most studies on T AIM are performed in adult mice, which have a small but substantial population of T AIM cells (~ 20% of total CD8 + T cells) [6][7][8][9][10][11][12][13]. In young (infant) mice, there is a larger fraction of T AIM cells (~ 35%) [23].…”

“…In aged mice, the percentage and absolute number of T AIM is again increased [9,11,28,71]. The precise mechanism that contributes to this increase is unknown, but also in older individuals T AIM cells depend on a combination of TCR and cytokine signaling.…”

“…For simplicity, we here refer to these cells as antigen-inexperienced memory T cells (T AIM ). T AIM cells constitute around 10-40% of total peripheral CD8 + T cells, indicating their potential importance in the immune system [6][7][8][9][10][11][12][13]. Two major CD8 + T AIM cell types have been described: innate memory and virtual memory cells.…”