Differential expression of human granzymes A, B, and K in natural killer cells and during CD8<sup>+</sup> T cell differentiation in peripheral blood

Bratke, Kai; Kuepper, Michael; Bade, Britta; Virchow, J. Christian; Luttmann, Werner

doi:10.1002/eji.200526122

Cited by 151 publications

(156 citation statements)

References 35 publications

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“…2A, 2D), probably because they have already been activated by some challenge without apparent symptom. Previous research showed that cytotoxic activity of the CD16 2 CD56 hi human NK cell subset increases significantly after type I IFN activation (29). This large potential increased space of cytotoxicity in CD16 2 CD56 hi NK cells may be due to their high levels of miR-378 and miR-30e, which provide large decreasing space to release many cytolytic effector mRNAs for translation.…”

Section: Discussionmentioning

confidence: 98%

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Wang

Zhang

et al. 2012

The Journal of Immunology

123

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NK cells are important innate immune cells with potent cytotoxicity that can be activated by type I IFN from the host once infected. How NK cell cytotoxicity is activated by type I IFN and then tightly regulated remain to be fully elucidated. MicroRNAs (miRNAs, or miRs) are important regulators of innate immune response, but the full scale of miRNome in human NK cells remains to be determined. In this study, we reported an in-depth analysis of miRNomes in resting and IFN-α–activated human NK cells, found two abundant miRNAs, miR-378 and miR-30e, markedly decreased in activated NK cells by IFN-α, and further proved that miR-378 and miR-30e directly targeted granzyme B and perforin, respectively. Thus, IFN-α activation suppresses miR-378 and miR-30e expression to release cytolytic molecule mRNAs for their protein translation and then augments NK cell cytotoxicity. Importantly, the phenomena are also confirmed in human NK cells activated by other cytokines and even in the sorted CD16+CD56dimCD69+ human NK cell subset. Finally, miR-378 and miR-30e were proved to be suppressors of human NK cell cytotoxicity. Taken together, our results reveal that downregulated miR-378 and miR-30e during NK cell activation are negative regulators of human NK cell cytotoxicity, providing a mechanistic explanation for regulation of NK cell function by miRNAs.

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Section: Discussionmentioning

confidence: 98%

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Wang

Zhang

et al. 2012

The Journal of Immunology

123

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“…1). 48, 100 However, both CD56 bright NK cells51 and CD161++ CD8+ T‐cells (including the MAIT cells)90 can upregulate GrB and perforin, and become efficient killer cells, after activation. For example, the CD56 bright NK cell population can kill activated autologous CD4+ T‐cells in MS 101, 102.…”

Section: Functional Similarities Between Nk Cell and Cd8+ T‐cell Subsetsmentioning

confidence: 99%

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

2018

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SummaryNew data in the worlds of both innate‐like CD8+ T‐cells and natural killer (NK) cells have, in parallel, clarified some of the phenotypes of these cells and also their associated functions. While these cells are typically viewed entirely separately, the emerging innate functions of T‐cells and, similarly, the adaptive functions of NK cells suggest that many behaviours can be considered in parallel. In this review we compare the innate functions of CD8+ T‐cells (especially mucosal‐associated invariant T‐cells) and those of NK cells, and how these relate to expression of phenotypic markers, especially CD161 and CD56.

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“…In the model by Sallusto et al [11], CCR7 + CD62L + antigen-experienced CD8 T cells circulate through secondary lymphoid tissue and are termed central memory cells, while CCR7 -CD62L +/-effector memory CD8 T cells migrate to peripheral sites. However, the process of T cell differentiation in response to antigen is highly complex, and other cell surface receptors such as CD7, CD27, CD28, CD45RA, CCR5 and CD127 can be used to identify functionally distinct subsets of effector and memory T cells [12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

et al. 2007

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Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5 + CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7 low , and produced IFN-c and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5 + CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5 + CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population. IntroductionCD8 T cells are lymphocytes of the adaptive immune system which recognize viral and bacterial peptides presented by MHC class I molecules and are indispensable in the control of many intracellular infections [1]. When appropriately stimulated by antigen presented by dendritic cells (DC) in secondary lymphoid tissues, they proliferate vigorously, become effector cells, and upon resolution of infection a small population of antigen-specific CD8 T cells are maintained as long-lived memory cells [2][3][4]. A primary effector mechanism of CD8 T cells is the killing of infected cells via the targeted release of the lytic effector molecules perforin and granzymes, and via expression of death receptors. However, there is significant functional heterogeneity in CD8 T cells and they are also efficient in producing anti-viral and pro-inflammatory cytokines [5][6][7][8]. The effector mechanisms used may depend on the pathogen and on the type of cell or tissue that is infected [8].CD8 T cell responses involve the differentiation of naive T cells into distinct types of effector and memory cells [2, 3,9]. One approach to analyse a T cell response is to examine the expression of receptors that mediate homing of T cells, such as CD62L, which binds to glycosylation-dependent cell adhesion molecule 1 on [4,20,21]. CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25]. CXCR5 + CD4 T cells, known as follicular homing T helper cells, are found in B cell follicles and contribute to the generation of effective humoral immune responses by supporting antibody production and isotype class switching [26,27]. However, some of the processes and mec...

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Differential expression of human granzymes A, B, and K in natural killer cells and during CD8⁺ T cell differentiation in peripheral blood

Cited by 151 publications

References 35 publications

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

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Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood

Cited by 151 publications

References 35 publications

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

Contact Info

Product

Resources

About

Differential expression of human granzymes A, B, and K in natural killer cells and during CD8⁺ T cell differentiation in peripheral blood

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles