Homeostasis of Naive and Memory T Lymphocytes

Abstract

Conventional CD4 + and CD8 + T lymphocytes comprise a mixture of naive and memory cells. Generation and survival of these T-cell subsets is under strict homeostatic control and reflects contact with self-major histocompatibility complex (MHC) and certain cytokines. Naive T cells arise in the thymus via T-cell receptor (TCR)-dependent positive selection to selfpeptide/MHC complexes and are then maintained in the periphery through self-MHC interaction plus stimulation via interleukin-7 (IL-7). By contrast, memory T cells are largely MHC-independent for their survival but depend strongly on stimulation via cytokines. Whereas typical memory T cells are generated in response to foreign antigens, some arise spontaneously through contact of naive precursors with self-MHC ligands; we refer to these cells as memory-phenotype (MP) T cells. In this review, we discuss the generation and homeostasis of naive T cells and these two types of memory T cells, focusing on their relative interaction with MHC ligands and cytokines.

Quantifying T Cell Cross-Reactivity: Influenza and Coronaviruses

“…The previous equation implies that the rate of homeostatic division per memory cell, σ M , does not depend on its TCR specificity. This is in line with our assumption that memory T cells are homeostatically regulated by cytokine signals, such as IL-7 or IL-15 [62,63,76,77].…”

“…An edge between a T cell clonotype and a peptide-MHC is drawn (or exists) if the given TCR clonotype recognizes the chosen peptide-MHC. We classified the set of peptide-MHCs according to whether they are derived from house-keeping proteins (or self), and we call them self-peptide-MHCs (self-pMHCs) [ 61 , 62 ], or whether they are virus-derived peptide-MHCs (VDPs) [ 63 , 64 ]. Figure 6 shows an example of a bipartite recognition network between T cell clonotypes and VDPs from two viruses, which will be later used in Section 5.1 to describe the dynamics of a T cell immune response to two heterologous viral infections.…”

“…For cells in the naive pool we assumed that homeostatic maintenance is ensured by self-pMHC presentation, which provides naive T cells with survival stimuli to divide [ 62 , 72 , 73 ]. If a naive cell receives a TCR-mediated signal from a VDP, in the context of a viral infection, this leads to naive T cell activation and differentiation into the effector T cell pool [ 63 , 74 , 75 ].…”

“…Thus, we expected the effector population to decline in the absence of pathogen. The memory population is homeostatically maintained separately from the naive or effector pools in a cytokine-mediated process [ 62 , 63 , 76 , 77 ].…”

“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

“…Different investigators have variously called the memory phenotype cells non-foreign antigen-derived memory (Kawabe et al, 2021), memory phenotype (Dobber et al, 1992;Haluszczak et al, 2009;White et al, 2017;Kawabe et al, 2020), innate memory (Kawabe et al, 2021), virtual memory (Akue et al, 2012;White et al, 2016) and yet others divide them into innate and virtual memory subsets (White et al, 2017). The CD44 + CD8 T cells have some of the positive attributes of true memory cells including more rapid cytokine production and response to some pathogens (Akue et al, 2012;Kawabe et al, 2020).…”