Natural Killer Cell Responses to Viral Infection

Brandstadter, Joshua D; Yang, Yiping

doi:10.1159/000324176

Cited by 168 publications

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“…Expansion of inhibitory KIRs occurred exclusively in donors carrying the cognate HLA class I ligands, whereas the presence of the putative ligand HLA-Bw4 was not necessary for the expansion of KIR3DS1-expressing NK cells. Our data show that previous infection with CMV does not alter the resting NK-cell receptor repertoire, but appears to modify how NK cells respond to re-exposure to CMV in vitro.Keywords: CMV r KIR r Natural killer cells Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are an important component of the immune system in the control of viral infection [1]. Unlike B and T cells, NK cells do not display rearranged receptors but instead are regulated by the integration of signaling from germline encoded activating and inhibitory receptors.…”

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confidence: 99%

“…Keywords: CMV r KIR r Natural killer cells Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are an important component of the immune system in the control of viral infection [1]. Unlike B and T cells, NK cells do not display rearranged receptors but instead are regulated by the integration of signaling from germline encoded activating and inhibitory receptors.…”

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Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

et al. 2012

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Patients carrying activating killer cell immunoglobulin-like receptor (KIR) genes are significantly protected from CMV-associated complications after solid organ or hematopoietic stem cell transplantation. Whether previous infection with CMV affects NK-cell function in healthy donors is unknown. We studied the KIR repertoire and alterations of KIR expression after in vitro exposure to CMV in 54 healthy donors. The expression of neither activating nor inhibitory KIRs was different at baseline between 23 seropositive and 31 seronegative donors. However, after co-culture of NK cells with CMV-infected fibroblast cells, expression of the inhibitory receptors KIR2DL1 and KIR2DL3 and the activating receptor KIR3DS1 significantly increased in CMV-seropositive donors. In CMVseronegative donors, changes were subtle and restricted to the subset of NK cells expressing NK-cell group antigen 2C (NKG2C). Expansion of inhibitory KIRs occurred exclusively in donors carrying the cognate HLA class I ligands, whereas the presence of the putative ligand HLA-Bw4 was not necessary for the expansion of KIR3DS1-expressing NK cells. Our data show that previous infection with CMV does not alter the resting NK-cell receptor repertoire, but appears to modify how NK cells respond to re-exposure to CMV in vitro.Keywords: CMV r KIR r Natural killer cells Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are an important component of the immune system in the control of viral infection [1]. Unlike B and T cells, NK cells do not display rearranged receptors but instead are regulated by the integration of signaling from germline encoded activating and inhibitory receptors. One important and incompletely characterized family of receptors are the killer cell immunoglobulin-like receptors (KIRs) [2]. KIRs are almost exclusively expressed on NK cells and encoded by 15 different gene loci, nine inhibitory iKIRs, and six activating aKIRs. The KIR genes cluster in chromosome 19, Correspondence: Prof. Martin Stern e-mail: sternm@uhbs.ch forming haplotypes composed of 7-11 individual KIR genes. The most common haplotype in Caucasians contains mostly iKIRs accompanied by a single or no aKIR gene and is called "A" haplotype [3]. Haplotypes containing more than one aKIR gene are collectively termed "B" haplotypes. Most iKIRs recognize HLA class I ligands and function as important receptors in the maintenance of NK-cell self-tolerance. In contrast, neither the ligands nor the function of most aKIRs have been established [4].We have recently shown in patients undergoing solid organ transplantation a protective effect of B haplotype genes regarding posttransplant CMV infection and reactivation [5,6]. * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2013. 43: 480-487 Innate immunity 481Similar studies have shown congruent results for donor activating KIR genotype in recipients of hematopoietic stem cell transplantation [7,8]. These data sugg...

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Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

et al. 2012

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“…NK cell functions are regulated by a balance between activating and inhibitory signals [29]. Their receptors recognizing the same MHC I or other ligands are polymorphic and highly homologous and can induce two opposite signals, but one of them dominates signal transduction.…”

Section: Dominant Receptors On Nk Cellsmentioning

confidence: 99%

Introductory Chapter: A Brief Overview on Natural Killer Cells

Aribi¹

2017

Natural Killer Cells

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Additional information is available at the end of the chapter IntroductionNatural killer (NK) cells represent about 5-15% of circulating lymphocytes [1] and belong to the innate immune system, in particular due to their invariant antigen receptors. Morphologically, as opposed to "small lymphocytes," most of them are typically large azurophilic granules containing lymphocytes (LGL) [2], characterized by high cytoplasmic:nuclear ratio. They have initially been referred to as k or null lymphocytes (non-B and non-T cells), with the highest cytotoxic capacity [3,4], because they lack conventional T-cell membrane markers and the surface membrane immunoglobulin (smIg) [5,6]. NK cells mediate resistance against intracellular pathogens, mainly viral-infected, bacteria-infected and protozoa-infected cells, and have the potential to restrain cancer and metastasis. They are also able to contribute to the activation and the regulation of the immune responses, as well as the orientation of adaptive immune responses [7,8]. More recently, NK cells were recognized as a subtype of type 1 innate lymphoid cells (ILC1), which express the transcription factor T-box expressed in T cells (T-bet), and deined by the production of the T helper cell type 1 (Th1)-associated cytokine interferon gamma (IFN-γ) and the inability to produce Th2 cell-associated and Th17 cell-associated cytokines [9]. As a result of collective work, this book has therefore the ultimate purpose to address the most fundamental aspects of NK cells, as well as their clinical applications for cancer immunotherapy. Lineage of NK cellsNK cells constitute a third lymphoid line derived from a common T-cell and B-cell bone marrow precursor. Unlike T cells, NK cells do not have a specialized diferentiating organ, are matured inside of bone marrow, and can develop even in athymic mice. The acquisition of their functions

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“…This elevation in systemic levels of the cytokine during acute disease stage has been linked with peak HIV viraemia [84] that is partly responsible for excessive immune activation experienced in HIV. It is also key to note that deficiencies in NK cell responses among HIV patients independent of CD4 + T cell depletion directs IFN-γ secretion [85], hence signifying the role of IFN-γ as a primary cytokine against HIV disease.…”

Section: Cytokines In Hivmentioning

confidence: 99%

Immunological Profiles in HIV Positive Patients with or without Opportunistic Infections and the Influence of Highly Active Antiretroviral Therapy: A Systematic Review and Update

Wambani¹,

Ng²,

Wm³

et al. 2016

J Clin Cell Immunol

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Background: Immune abnormalities are occasioned during HIV infection consequently predisposing opportunistic infections. In part, these derangements result from impaired expression of a number of immunologically important cytokines. However, exact mechanisms behind HIV infectivity on immune system maturation and cytokine production is not well elucidated, more specifically during treatment with HAART. As such, this review compiles data from various studies with the aim of understanding alterations in cytokine network during the course of HIV infection, while assessing the impact of antiretroviral treatment towards cytokine expression.

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Natural Killer Cell Responses to Viral Infection

Cited by 168 publications

References 111 publications

Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

Introductory Chapter: A Brief Overview on Natural Killer Cells

Immunological Profiles in HIV Positive Patients with or without Opportunistic Infections and the Influence of Highly Active Antiretroviral Therapy: A Systematic Review and Update

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