Virtual Memory CD8<sup>+</sup> T Cells: Origin and Beyond

Viano, María Estefanía; Baez, Natalia Soledad; Savid-Frontera, Constanza; Lidon, Nicolás Leonel; Hodge, Deborah L.; Herbelin, André; Gombert, Jean‐Marc; Barbarin, Alice; Rodríguez-Galán, María Cecilia

doi:10.1089/jir.2022.0053

Cited by 3 publications

(3 citation statements)

References 109 publications

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“…Memory Tc1 cells retain the cytotoxic phenotype of effector Tc1 cells 35 and readily produce IFN-γ upon reactivation 36 . Even in antigen-naive mice, a population of memory-like Tc1 cells, namely, CD44 hi CD122 hi CD8 + T cells, which are different from naïve T cells, can rapidly produce IFN-γ in response to TCR stimulation [37][38][39] . These cells exhibit a distinct epigenetic pattern on the Ifng promoter, suggesting that cytokine production may be regulated at the transcriptional level independent of previous antigen exposure-induced cell priming.…”

Section: Cytotoxic Cd8 + T Cells (Tc1 Cells)mentioning

confidence: 99%

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Koh,

Lee,

Kwak

et al. 2023

Exp Mol Med

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CD8 T cells play crucial roles in immune surveillance and defense against infections and cancer. After encountering antigenic stimulation, naïve CD8 T cells differentiate and acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic T cells, characterized by their ability to produce effector cytokines and release cytotoxic granules to directly kill target cells, have been recognized as the constituents of the predominant effector T-cell subset. However, emerging evidence suggests distinct subsets of effector CD8 T cells that each exhibit unique effector functions and therapeutic potential. This review highlights recent advancements in our understanding of CD8 T-cell subsets and the contributions of these cells to various disease pathologies. Understanding the diverse roles and functions of effector CD8 T-cell subsets is crucial to discern the complex dynamics of immune responses in different disease settings. Furthermore, the development of immunotherapeutic approaches that specifically target and regulate the function of distinct CD8 T-cell subsets holds great promise for precision medicine.

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Section: Cytotoxic Cd8 + T Cells (Tc1 Cells)mentioning

confidence: 99%

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Koh,

Lee,

Kwak

et al. 2023

Exp Mol Med

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“…In addition, ex-T RM cells do not usually express CD69, although epigenetic features of previous tissue residency may inform the future identification of a core phenotype 119 . Other memory subsets have not been included here for reasons of clarity, but a global classification should encompass a more nuanced view of T SCM cells 51 , refined to incorporate the dichotomy between exhaustion and functionality 47 , and virtual memory cells 129 within a flexible and integrated structure. Current data nonetheless permit an immediate revision to the simplistic linear model that is biologically instructive and eminently tractable using basic flow cytometry (Figure 3).…”

Section: Integrated Human Classification Modelmentioning

confidence: 99%

Human circulating and tissue-resident memory CD8+ T cells

et al. 2023

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Our current knowledge of human memory CD8 + T cells is derived largely from studies of the intravascular space. However, emerging data are starting to challenge some of the dogmas based on this work, suggesting that a conceptual revision may be necessary. In this review, we provide a brief history of the field and summarize the biology of circulating and tissueresident memory CD8 + T cells, which are ultimately responsible for effective immune surveillance. We also incorporate recent findings into a biologically integrated model of human memory CD8 + T cell differentiation. Finally, we address how future innovative human studies could improve our understanding of anatomically localized CD8 + T cells to inform the development of more effective immunotherapies and vaccines, the need for which has been emphasized by the global struggle to contain SARS-CoV-2.

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“…For instance, TVM cells have been implicated in various pathogenic conditions, including aging, infection, and cancer 23 . Research on human TVM cells is interesting but facing challenges, such as the difficulties in phenotypical characterization and heterogeneity of the cell subset 74 . Using single-cell transcriptional analysis and flow cytometric validation, we found that CD45RA and EOMES were highly co-expressed in panKIR and/or NKG2A positive CD8+ T cells, which unifies the two commonly used strategies to identify human TVM cells.…”

Section: Discussionmentioning

confidence: 99%

Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

Wang,

Zhen,

et al. 2023

Commun Biol

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CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.

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Virtual Memory CD8⁺ T Cells: Origin and Beyond

Cited by 3 publications

References 109 publications

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Human circulating and tissue-resident memory CD8+ T cells

Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

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Virtual Memory CD8+ T Cells: Origin and Beyond

Cited by 3 publications

References 109 publications

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Human circulating and tissue-resident memory CD8+ T cells

Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

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Product

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Virtual Memory CD8⁺ T Cells: Origin and Beyond