Innate and virtual memory T cells in man

Immunological memory exists so that following infection an expanded population of pathogen-specific lymphocytes can rapidly and efficiently control infection in the case of reexposure. However, in the case of CD8+ T lymphocytes, a population of unconventional CD44+CD122+ virtual memory T cells (TVM) has been described that possesses many, though not all, features of “true memory” T cells, without the requirement of first encountering cognate antigen. Here, we demonstrate a role for regulatory T cell-mediated restraint of TVM at least in part through limiting IL-15 trans-presentation by CD11b+ dendritic cells. Further, we show that keeping TVM in check ensures development of functional, antigen-specific “true” memory phenotype CD8+ T cells that can assist in pathogen control upon reexposure.

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Forget ‘ME’ not virtual memory T cells

Nature Immunology ◽

10.1038/s41590-020-0668-7 ◽

2020 ◽

Vol 21 (5) ◽

pp. 499-500 ◽

Cited By ~ 1

Author(s):

Mark A. Daniels ◽

Emma Teixeiro

Keyword(s):

T Cells ◽

Memory T Cells ◽

Virtual Memory

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

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03912-9 ◽

2021 ◽

Author(s):

Eliza Mari Kwesi-Maliepaard ◽

Heinz Jacobs ◽

Fred van Leeuwen

Keyword(s):

T Cells ◽

Epigenetic Regulation ◽

Cd8 T Cells ◽

Memory T Cells ◽

Virtual Memory ◽

Current Understanding ◽

Memory Cd8 T Cells ◽

Foreign Antigen ◽

Memory Phenotype ◽

The Past

AbstractConventional CD8+ memory T cells develop upon stimulation with foreign antigen and provide increased protection upon re-challenge. Over the past two decades, new subsets of CD8+ T cells have been identified that acquire memory features independently of antigen exposure. These antigen-inexperienced memory T cells (TAIM) are described under several names including innate memory, virtual memory, and memory phenotype. TAIM cells exhibit characteristics of conventional or true memory cells, including antigen-specific responses. In addition, they show responsiveness to innate stimuli and have been suggested to provide additional levels of protection toward infections and cancer. Here, we discuss the current understanding of TAIM cells, focusing on extrinsic and intrinsic molecular conditions that favor their development, their molecular definitions and immunological properties, as well as their transcriptional and epigenetic regulation.

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Bystanders or real players: virtual memory T cells keep chronic infections in check

Cellular and Molecular Immunology ◽

10.1038/s41423-020-0469-9 ◽

2020 ◽

Vol 17 (8) ◽

pp. 797-798

Author(s):

Kylie M. Quinn ◽

Tabinda Hussain

Keyword(s):

T Cells ◽

Memory T Cells ◽

Virtual Memory ◽

Chronic Infections

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Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells

10.1101/202218 ◽

2017 ◽

Cited By ~ 1

Author(s):

Ales Drobek ◽

Alena Moudra ◽

Daniel Mueller ◽

Martina Huranova ◽

Veronika Horkova ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Fate ◽

Memory T Cells ◽

Autoimmune Diabetes ◽

Virtual Memory ◽

Naive T Cells ◽

Memory Cd8 T Cells ◽

Foreign Antigen ◽

Naïve T Cells

AbstractVirtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute for 10-20% of all peripheral CD8+ T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing TCR repertoires and using retrogenic monoclonal T-cell populations, we show that virtual memory T cells originate exclusively from strongly self-reactive T cells. Moreover, we show that the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T-cell clones. We propose a so far unappreciated peripheral T-cell fate decision checkpoint that eventually leads to the differentiation of highly self-reactive T cells into virtual memory T cells. This underlines the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they do not show higher capacity to induce autoimmune diabetes than naïve T cells. Thus, virtual memory T cells are not generally more responsive than naïve T cells, because their activity highly depends on the immunological context.SummaryWe conclude that virtual memory T cells are formed from self-reactive CD8+ T cells in a process regulated by CD8-Lck stoichiometry. Despite their self-reactivity and partial memory differentiation program, virtual memory T cells did not show a strong autoimmune potential.

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