CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells

Kurioka, Ayako; Cosgrove, Cormac; Simoni, Yannick; Wilgenburg, Bonnie van; Geremia, A; Björkander, Sophia; Sverremark-Ekström, Eva; Thurnheer, Christine; Günthard, Huldrych F.; Khanna, Nina; Walker, L J; Arancibia‐Cárcamo, Carolina V.; Newell, Evan W.; Willberg, Christian; Klenerman, Paul

doi:10.3389/fimmu.2018.00486

Cited by 90 publications

(92 citation statements)

References 62 publications

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“…Given the wide diversity of conventional and non-classical T cells now recognised 24 , many of which share common transcriptional programmes 40,41 we applied a comparative approach 42 to analyse the phenotype of MAIT cells, overcoming significant methodological hurdles to compare our RNA sequencing data directly with older microarray expression data in the ImmGen dataset. Activated MAIT cells were most similar to activated invariant iNKT cells, as might be expected from the similarities in surface markers and functional phenotype 5,24,43 .…”

Section: Discussionmentioning

confidence: 99%

Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality

Hinks

Marchi

Jabeen

et al. 2018

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22Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells 23 conserved across mammalian species, including mice and humans. By sequencing RNA 24 from sorted MR1-5-OP-RU tetramer + cells derived from either human blood or murine 25 lungs, we define the basic transcriptome of an activated MAIT cell in both species and 26 demonstrate how this profile changes during resolution and reinfection phases of infection. 27We observe strong similarities between MAIT cells in humans and mice. Compared with 28 previously published T cell transcriptomes, MAIT cells displayed most similarity to iNKT 29 cells when activated, but to gd T cells, after resolution of infection. In both species 30 activation leads to strong expression of pro-inflammatory cytokines and chemokines, and 31 also a strong tissue repair signature, recently described in murine commensal-specific H2-32 M3-restricted T cells. These data define the requirements for, and consequences of, MAIT 33 cell activation, revealing a tissue repair phenotype expressed upon MAIT cell activation in 34 both species. 35 36 Key words 37 Mucosal-associated invariant T cell, T cell, transcriptome, MHC-related protein 1, 38 activation, lung, human, mouse, riboflavin. 39 40 3 Mucosal-associated invariant T (MAIT) cells are innate-like T cells which express a 'semi-41 invariant' ab T cell receptor (TCR) and recognise metabolic derivatives of riboflavin 42 biosynthesis 1-3 presented on the restriction molecule major histocompatibility complex 43 (MHC)-related protein-1 (MR1) 4,5 . These antigens, which include the potent MAIT cell 44 ligand 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) 6 , are produced by a 45 wide variety of bacteria, mycobacteria and yeasts 1,7 , but are absent from mammals, and 46 therefore allows host -pathogen discrimination. MAIT cells have a strong pro-47 Our data reveal strong similarities between MAIT cells in humans and in mice at a 64 transcriptional level, show that MAIT cells displayed the closest similarities to invariant 65 natural killer T (iNKT) cells when activated, but after resolution of infection were more 66 comparable to gd T cells, and reveal a previously unknown tissue repair phenotype 67 expressed upon MAIT cell activation in both species. 68 69 Results 70 Activation requirements of MAIT cells in vivo 71First we aimed to test, systematically, the activation requirements of MAIT cells in vivo in 72 mouse lungs. We have previously shown that pulmonary MAIT cell frequencies in mice 73 can be markedly enhanced by intranasal administration of 5-OP-RU if it is co-administered 74 with S-[2,3-bis(palmitoyloxy)propyl] cysteine (Pam2Cys), CpG ODN 1668 or 75 polyinosinic:polycytidylic acid (poly I:C), which are agonists for TLR2/6, TLR9 and 76 TLR3, respectively. We therefore investigated agonists for each of the murine TLRs, using 77 the maximum doses presented in a literature review of previous studies of these 78 compounds. All animals received the relevant TLR intranasally on day 0. In experimental 79 animals...

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Section: Discussionmentioning

confidence: 99%

Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality

Hinks

Marchi

Jabeen

et al. 2018

Preprint

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“…Assaying cells from controllers in-vitro showed that NK cells were equivalent to CD8 + T cells in inhibiting viral replication 95 ; however recent work has demonstrated CD11b + CD57 - CD161 + Siglec-7 + NK cells to be more abundant in elite controllers compared to those who progress 96 . The proliferating NK cells measured here also express high levels of CD161 ( KLRB1 ), associated with the production of IFN- γ in response to IL-12 and IL-18 97 . Antigen specific expansion of cytotoxic NK cells has been shown to occur in hCMV 98,99 , hantavirus 100 , and SIV 101 as a “memory-like” response; however, we do not measure changes in NKG2C ( KLRC1 ) here.…”

Section: Discussionmentioning

confidence: 80%

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Kazer

Aicher

Muema

et al. 2019

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30Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and 31 cooperativity of the evolving host response to infection are not well defined. Here, we apply single-32 cell RNA-sequencing to longitudinally profile pre-and immediately post-HIV infection peripheral 33 immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a 34 strong transcriptional interferon response integrated across most cell types, with subsequent pro-35 inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With 36 longitudinal sampling, we nominate key intra-and extracellular drivers that induce these 37 programs, and assign their multi-cellular targets, temporal ordering, and duration in acute 38 infection. Two individuals studied developed spontaneous viral control, associated with initial 39 elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated 40 proliferating natural killer (NK) cell subset. Our study presents a unified framework for 41 characterizing immune evolution during a persistent human viral infection at single-cell resolution, 42 and highlights programs that may drive response coordination and influence clinical trajectory. 43 44 54Recently, high-throughput single-cell RNA-sequencing (scRNA-Seq) has emerged as a 55 powerful tool to characterize, transcriptome-wide, complex human systems in health and disease 56 at single-cell resolution [3][4][5][6][7][8][9] . When applied to a collection of samples across a disease setting, this 57 approach provides a platform for investigating cell types, states, interactions, and drivers 58 associated with that disease; this information can be used to develop testable hypotheses on 59 therapeutic modulations that may ameliorate disease state 7,8 . Meanwhile, within an individual, 60longitudinal sampling provides an opportunity to decipher, at unprecedented resolution and 61 absent potentially confounding inter-individual variability 7 , shifts in these same variables, and to 62 3 associate observed changes with internal or external perturbations 10-12 . Such sampling of a host's 63 exposure to a pathogen could provide foundational insights into essential cellular response 64 features and their coordination, empowering the rational design of improved prophylactic 65 interventions. 66Illustratively, a better understanding of the interplay between innate and adaptive immune 67 responses at the very earliest stages of a viral infection, and its impact on long-term disease, 68 could reveal principles to accelerate prevention efforts. Human Immunodeficiency Virus (HIV) has 69 been the subject of thorough study, and thus is a well-considered model system for examining 70 host responses to a pathogen. Moreover, although the development of antiretroviral therapy 71 (ART) 13 , as well as implementation of pre-exposure prophylaxis (PrEP) 14 and combination 72 prevention efforts, has improved the lives of persons living with HIV, increased life expectancie...

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“…Patients had a significantly higher proportion of NK cells bearing markers associated with NK immaturity (CD25, CD27, CD127 and HLA-DR) 34,35,36,37 and a significantly lower proportion of NK cells bearing markers associated with NK maturity (CD45RA and CD57) 38,39 . No difference was observed in the proportion of NK cells expressing the adhesion molecule CD11b 40 , the adhesion molecule and ectoenzyme CD38 41 nor CD161, expressed by a distinct subtype of pro-inflammatory NK cells 42 . There was also no difference in expression of the chemokine receptor CXCR3 which is required for NK cell accumulation in tumors 43 .…”

Section: Nk Cells In Patients Are Shifted To An Immature Phenotypementioning

confidence: 82%

Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

Syrimi

Khan

Murray

et al. 2020

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Syrimi et al. High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by ageOne Sentence Summary: High dimensional analysis of systemic immunity in pediatric cancer patients reveals clinically relevant immune changes in NK and T-cells that vary with patient age. Abstract:Systemic immunity plays important roles in cancer immune surveillance and therapy but little is known about the immune status of healthy children or children with cancer. We performed a high dimensional single cell analysis of systemic immunity in pediatric cancer patients and agematched healthy children. In young children with cancer (age <8years) NK cells were decreased in frequency, maturity, expression of perforin and granzyme-B, and were less cytotoxic in ex vivo assays. NK cell activity was restored after in vitro culture with interleukin-2. In contrast, older children with cancer (>8 years old) had decreased naive CD4 and CD8 T-cells with concomitant increases in effector memory and T effector memory RA-revertant (TEMRA) Tcells. These immunological changes in pediatric cancer patients are relevant to the better understanding of how cancers diagnosed in childhood interact with systemic immunity and could inform the development and application of effective immune-modulating therapies in the pediatric population. Syrimi et al. High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by age

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CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells

Cited by 90 publications

References 62 publications

Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality

Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

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