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Revisiting the role of human memory CD8+ T cells in immune surveillance

Cellular & Molecular Immunology volume 19, pages 1319–1321 (2022)Cite this article

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Virtual memory T (TVM) cells were first described 13 years ago in mice as a specialized subset of CD8+ T cells that are semi-differentiated, antigen-naïve, and characterized by a memory phenotype and functionality [1]. A putative TVM cell subset has been identified in humans for its presence in cord blood, indicating that it does not necessarily have to be antigen experienced [2]. Although phenotypically different (CD44hi CD62L+ CD49dlow in mice and CD45RA+ killer-cell immunoglobulin-like receptor (KIR)/NKG2A+ in humans), TVM cells exhibit similar functionality in mice and humans; that is, they are cytokine-responsive and exert rapid cytotoxicity [3]. Likewise, there are several studied CD8+ T-cell subpopulations that are functionally reminiscent of TVM cells, such as innate-like CD8+ T cells, natural killer (NK)-like CD8+ T cells, and memory phenotype CD8+ T cells. The molecular conditions underlying their development, definition, and immunological properties have been previously discussed [3]. Here, we mainly focus on the origin, activation, and effector functions of TVM cells, their clinical relevance, and the potential application of TVM cells in developing novel therapeutic approaches.

Recent studies have highlighted that the phenotype and functionality of TVM cells are influenced by their distinctive metabolic characteristics. TVM cells show a unique effector-memory mixed metabolic profile and are capable of relying on both glycolysis and oxidative phosphorylation [9]. Compared with naïve and true memory cells, TVM cells exhibit the highest spare respiratory capacity (SRC, which reflects the mitochondrial capacity that a cell holds in reserve). SRC levels correlate with IL-15 sensitivity and Bcl-2 expression and are therefore associated with the function and survival capacity of TVM cells [10]. Moreover, these metabolic features are retained during aging, resulting in quantitative accumulation with the functional senescence of TVM cells in aged individuals [9,10,11]. However, most of these findings come from investigations conducted in mice, and whether human TVM cells share the same or have distinct metabolic features requires further study.

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Acknowledgements

We acknowledge funding support from the National Natural Innovation Fund (Project 81721002).

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Authors and Affiliations

  1. Medical School of Chinese People’s Liberation Army (PLA), Beijing, China

    You-Yuan Wang, Wei Hu, Fu-Sheng Wang & Chao Zhang

  2. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China

    You-Yuan Wang, Wei Hu, Fu-Sheng Wang & Chao Zhang

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  1. You-Yuan Wang
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Y-YW, WH, and CZ wrote the manuscript and constructed the figures. F-SW revised the manuscript and figures.

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Correspondence to Fu-Sheng Wang or Chao Zhang.

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Wang, YY., Hu, W., Wang, FS. et al. Revisiting the role of human memory CD8+ T cells in immune surveillance. Cell Mol Immunol 19, 1319–1321 (2022). https://doi.org/10.1038/s41423-022-00900-2

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