KLRG1—more than a marker for T cell senescence

Henson, Sian M.; Akbar, Arne N.

doi:10.1007/s11357-009-9100-9

Cited by 152 publications

(133 citation statements)

References 58 publications

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“…Although NK cells were the focus of this study, it is important to investigate the role of other immune cells in the control of metastasis, either in conjunction or independent of NK cells. The role of cytotoxic T cells might be particularly important, as subpopulations as these cells also express KLRG1 and CRTAM receptors that recognize E-cad and CADM1 (55,56).…”

Section: Discussionmentioning

confidence: 99%

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Chockley

Chen

et al. 2018

Journal of Clinical Investigation

116

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Section: Discussionmentioning

confidence: 99%

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Chockley

Chen

et al. 2018

Journal of Clinical Investigation

116

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“…In addition, an altered TCR repertoire with age (19) during priming, changing the rate of differentiation or proportion of different memory T cell subsets. Finally, other cell-intrinsic or external factors such as inherent T cell senescence (51)(52)(53) or Tregs (23,24) could influence the initial development of T cell memory in aged mice. It is possible that more than one of these mechanisms contributes to changes in CD8 T cell memory with age.…”

Section: Discussionmentioning

confidence: 99%

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Decman

Laidlaw

DiMenna

et al. 2010

The Journal of Immunology

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Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity.

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“…The process of intranuclear staining for T-bet and Eomes, and the (25), hampers cell sorting and stimulation assays. Therefore, we defined the functional profiles of the surface marker-or TF-defined subsets by determining the expression of a number of key molecules predictive for functional potential: IL-7R␣ (memory marker, mediator of homeostatic proliferation) (13,36), granzyme K (effector memory marker, mediator of apoptosis, triggers cytokine release and functions through noncytotoxic inhibition of viral replication) (37-39), KLRG1 (coinhibitory receptor, negative regulator of fully differentiated T cells) (40,41), and granzyme B (effector marker, mediator of apoptosis) (37,38). First, we determined the associations between the expression of these molecules and the CD45RA/CCR7/CD28/CD27 phenotypes in both healthy individuals and untreated HIV-1-infected individuals.…”

Section: T-bet and Eomes Expression Levels Are Indicators Of The Funcmentioning

confidence: 99%

Infection History Determines the Differentiation State of Human CD8 ⁺ T Cells

Aalderen

Remmerswaal

Verstegen

et al. 2015

J Virol

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After the resolution of the acute phase of infection, otherwise quiescent antigen-experienced CD8؉ T cells confer rapid protection upon reinfection with viral pathogens or, in the case of persistent viruses, help to maintain control of the infection. Depending on the type of virus, antigen-specific CD8 ؉ T cells have distinct traits, ranging from typical memory cell properties in the case of rapidly cleared viruses to immediate effector functions for persistent viruses. We here show that both the differentiation stage, defined by the expression of cell surface markers, such as CD45RA, CCR7, CD28, and CD27, and distinct expression levels of T-bet and eomesodermin (Eomes) predict the functional profile of antigen-experienced CD8 ؉ T cells. Furthermore, virusspecific CD8؉ T cells targeting different respiratory syncytial virus-, influenza A virus-, Epstein-Barr virus (EBV)-, human cytomegalovirus (hCMV)-, and HIV-1-specific epitopes adopt distinct T-bet and Eomes expression patterns that appear to be installed early during the primary response. Importantly, the associations between surface phenotype, T-bet/Eomes expression levels, and the expression of markers that predict CD8؉ T-cell function change according to viral infection history, particularly against the background of HIV-1 and, to lesser extent, of human cytomegalovirus and/or Epstein-Barr virus infection. Thus, the functionality of human antigen-experienced CD8 ؉ T cells follows at least two dimensions, one outlined by the surface phenotype and another by the T-bet/Eomes expression levels, which are determined by previous or persistent viral challenges. IMPORTANCE Functional human CD8؉ T-cell subsets have been defined using surface markers like CD45RA, CCR7, CD28, and CD27. However, the induction of function-defining traits, like granzyme B expression, is controlled by transcription factors like T-bet and Eomes. Here, we describe how T-bet and Eomes levels distinctly relate to the expression of molecules predictive for CD8؉ T-cell function in a surface phenotype-independent manner. Importantly, we found that central memory and effector memory CD8 ؉ T-cell subsets differentially express T-bet, Eomes, and molecules predictive for function according to viral infection history, particularly so in the context of HIV-1 infection and, to lesser extent, of latent EBV-and/or hCMV-infected, otherwise healthy adults. Finally, we show that the distinct phenotypes and T-bet/Eomes levels of different virus-specific CD8 ؉ T-cell populations are imprinted early during the acute phase of primary infection in vivo. These findings broaden our understanding of CD8 ؉ Tcell differentiation. T he process of viral and host coevolvement has selected for antiviral CD8ϩ T-cell responses that are successful in ensuring survival of the host. As an apparent consequence, human circulating virus-specific CD8 ϩ T cells display distinct phenotypic and functional properties according to the virus or viral proteins they target (1-3). Acute viruses, such as respiratory syncytial vir...

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KLRG1—more than a marker for T cell senescence

Cited by 152 publications

References 58 publications

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Infection History Determines the Differentiation State of Human CD8 ⁺ T Cells

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KLRG1—more than a marker for T cell senescence

Cited by 152 publications

References 58 publications

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Infection History Determines the Differentiation State of Human CD8 + T Cells

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Infection History Determines the Differentiation State of Human CD8 ⁺ T Cells