Opinion: Virtual memory CD8 T cells and lymphopenia-induced memory CD8 T cells represent a single subset: Homeostatic memory T cells

Pribikova, Michaela; Moudrá, Alena; Štěpánek, Ondřej

doi:10.1016/j.imlet.2018.09.003

Cited by 13 publications

(15 citation statements)

References 54 publications

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“…The proliferation by naïve CD8 T cells in septic hosts suggests that CD8 T cells are proliferating in response to the lymphopenic environment. Indeed, naive cells undergo antigen-independent proliferation in other lymphopenic environments, such as Rag -/- or irradiated hosts, wherein they adopt conventional markers of antigen experience along with some effector functionality ( Cheung et al, 2009 ; Pribikova et al, 2018 ; Unsinger et al, 2009 ; White et al, 2017 ). Thus, it may be relevant to consider how the proliferation of these cells also alter the composition of the memory CD8 T cell compartment and shapes host response to subsequent infection for which they may be specific.…”

Section: Discussionmentioning

confidence: 99%

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Jensen

McGonagill

et al. 2021

eLife

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The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.

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Section: Discussionmentioning

confidence: 99%

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Jensen

McGonagill

et al. 2021

eLife

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“…For these reasons, some researchers proposed additional or alternative markers of the CD8 + CD122 + population such as CD44 [43, 44], CD62L [44], CXCR3 [38], PD‐1 [44, 45], CD38 [46], and Ly49 [43, 47, 48]. It is also clear that CD8 + CD122 + T cells overlap, at least partially, with antigen inexperienced memory‐like T (AIMT) cells (alias virtual memory T cells), that is, CD8 + T cells that have memory phenotype despite no previous antigen exposure [42, 49, 50].…”

Section: Cd8+ Cd122+ T Cellsmentioning

confidence: 99%

CD8⁺ Tregs revisited: A heterogeneous population with different phenotypes and properties

et al. 2021

Self Cite

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Regulatory T cells (Tregs) play a key role in the peripheral self‐tolerance and preventing autoimmunity. While classical CD4+ Foxp3+ Tregs are well established, their CD8+ counterparts are still controversial in many aspects including their phenotypic identity and their mechanisms of suppression. Because of these controversies and because of only a limited number of studies documenting the immunoregulatory function of CD8+ Tregs in vivo, the concept of CD8+ Tregs is still not unanimously accepted. We propose that any T‐cell subset considered as true regulatory must be distinguishable from other cell types and must suppress in vivo immune responses via a known mechanism. In this article, we revisit the concept of CD8+ Tregs by focusing on the characterization of individual CD8+ T‐cell subsets with proposed regulatory capacity separately. Therefore, we review the phenotype and function of CD8+ FOXP3+ T cells, CD8+ CD122+ T cells, CD8+ CD28low/− T cells, CD8+ CD45RClow T cells, T cells expressing CD8αα homodimer and Qa‐1‐restricted CD8+ T cells to show whether there is sufficient evidence to establish these subsets as bona fide Tregs. Based on the intrinsic ability of CD8+ Treg subsets to promote immune tolerance in animal models, we elaborate on their potential use in clinics.

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“…As a result, the current model of T VM ‐cell generation is that IL‐15 signaling in the neonatal periphery drives lymphopenia‐induced proliferation and semi‐differentiation in modestly self‐reactive naïve CD8 T cells, to elicit a cytokine‐driven, partial memory phenotype . It has been proposed that T VM cells are essentially equivalent to lymphopenia‐induced proliferation CD8 T (T LIP ) cells, which are semi‐differentiated CD8 T cells generated after transfer of naïve CD8 T cells into lymphopenic mice (Table ), although this is yet to be experimentally demonstrated.…”

Section: Refining the Model Of Tvm‐cell Generationmentioning

confidence: 99%

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

Hussain

Quinn

2019

Immunol Cell Biol

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Immunological memory is a phenomenon where the immune system can respond more rapidly to pathogens and immunological challenges that it has previously encountered. It is defined by several key hallmarks. After an initial encounter, immune cells (1) expand and (2) differentiate to form memory cell populations. Memory cells are (3) long‐lived and (4) facilitate more rapid immune responses to subsequent infection because of (i) an increase in cell number, (ii) a decrease in the signaling threshold required for entry into cell cycle or effector function and (iii) localization of cells to tissue sites for surveillance. Classically, immunological memory has been antigen specific but it is becoming apparent that mechanisms of immunological memory can be co‐opted by innate or antigen‐inexperienced immune cells to generate heterogeneity in immune responses. One such cell is the virtual memory CD8 T (TVM) cell, which is a semi‐differentiated but antigen‐naïve CD8 T‐cell population. This review will summarize current knowledge of how TVM cells are generated, their memory‐like hallmarks, how they are maintained during steady state, infection and aging, and propose a model to integrate key signaling pathways during their generation.

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Opinion: Virtual memory CD8 T cells and lymphopenia-induced memory CD8 T cells represent a single subset: Homeostatic memory T cells

Cited by 13 publications

References 54 publications

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

CD8⁺ Tregs revisited: A heterogeneous population with different phenotypes and properties

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

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Opinion: Virtual memory CD8 T cells and lymphopenia-induced memory CD8 T cells represent a single subset: Homeostatic memory T cells

Cited by 13 publications

References 54 publications

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

CD8+ Tregs revisited: A heterogeneous population with different phenotypes and properties

Similar but different: virtual memory CD8 T cells as a memory‐like cell population

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CD8⁺ Tregs revisited: A heterogeneous population with different phenotypes and properties