Stimulation of Human γδ T Cells by Nonpeptidic Mycobacterial Ligands

Constant, Patricia; Davodeau, François; Peyrat, Marie-Alix; Poquet, Yannick; Puzo, Germain; Bonneville, Marc; Fournié, Jean‐Jacques

doi:10.1126/science.8146660

Cited by 660 publications

(500 citation statements)

References 23 publications

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“…This subset is markedly expanded during the first phase of TB infection in the mouse [84] and has been suggested to be involved as a first line of defence recognizing heat shock antigens [85], a 10-14 kDa antigen released from the bacilli by heat treatment [86], or low mass non-peptidic ligands on the surface of the macrophage [87]. Recent evidence strongly in favour of the latter observation indicates that the ligands recognized are phosphorylated nucleotide conjugates containing thymidine and with an estimated molecular mass of 500-600 daltons [88]. The phosphate component seems to be essential and cleavage completely abrogates the stimulatory activity for gd cells [89].…”

Section: Host Responses and Antigens Involved In Protective Immunity mentioning

confidence: 99%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Andersen P. Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis. Scand J Immunol 1997;45:115-131 Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

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Section: Host Responses and Antigens Involved In Protective Immunity mentioning

confidence: 99%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Section: Introductionmentioning

confidence: 99%

“…In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].During mouse NK cell development, lineage markernegative bone marrow progenitors develop progressively into CD122 + NK1.1 -DX5 -committed NK progenitors, CD122 + NK1.1 + DX5 -immature NK cells and finally CD122 + NK1.1 + DX5 + mature NK cells, all of which can be found in the bone marrow. At the immature DX5 -stage, NK cells express multiple NK receptors including CD94/NKG2, NKG2D and NKp46, but are unable to perform granule-mediated cytotoxicity [21][22][23].…”

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confidence: 99%

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

et al. 2007

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NK cells and cd T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor d locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germline transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from "bona fide" NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRcd but high intracellular CD3, define these cells as cd T cells. "NK-like cd T cells" are CD127 + , have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-c in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like cd T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRcd engagement as a means of acquiring NK-like function. IntroductionClassification of NK cells and some cd T cell subsets as innate immune cells is argued by their recognition and response to self ligands and microbial molecules without any requirement for prior specific immunization [1][2][3][4][5]. NK cells are mediators of immunity against various infectious diseases and tumor cells, performing direct cell-mediated cytotoxicity and producing cytokines in response to cell-associated and soluble stimuli [6,7]. They additionally shape adaptive immune responses, mainly through the production of cytokines [8]. Their activation is regulated through germ-line-encoded receptors including NKG2D, the natural cytotoxicity receptors and inhibitory receptors for MHC class I, many of which recognize self-encoded ligands [9][10][11]. Most cd T cell subsets are unconventional T cells that -similar to CD1d-restricted Va14i NKT cells, MR1-restricted MAIT cells and certain populations of CD8 + T cells -are not restricted to classical MHC class I-or MHC class II-bearing specific peptides [2,3]. They have heterogeneous effector functions associated with differential TCRcd usage. Roles have been described in immunity against infectious pathogens and tumors [12] and cd T cells have been strongly implicated in immunosuppressive regulation of the immune system and in the process of wound healing [13,14]. Using TCR transfer experiments, or direct ligand binding, TCRcd ligands have been described for a small number of subsets [5]. In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].Du...

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“…This response is similar, in part, to an antigen driven response, except it occurs with a large fraction of the naive γδ T cell population. Also, though it is widely accepted that γδ T cells recognize microbial nonpeptidic phosphorylated molecules [16][17][18] and alkylamines [19,20] in a TCRdependent manner, LPS has not, to our knowledge, been described as a TCR ligand. While we have not precisely determined the mechanism of LPS detection, transcripts encoding many TLRs and other pattern recognition proteins are readily detected in γδ T cells [15,[21][22][23][24][25].…”

Section: Discussionmentioning

confidence: 93%

Mucosal lymphatic-derived γδ T cells respond early to experimental Salmonella enterocolitis by increasing expression of IL-2Rα

Hedges

Buckner

Rask

et al. 2007

Cellular Immunology

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To better understand the roles of γδ T cells in mucosal infection, we utilized Salmonella enterica serovar Typhimurium (Salmonella serovar Typhimurium) infection in cattle as it closely approximates Salmonella serovar Typhimurium-induced enterocolitis in humans. Protein and gene expression in αβ and γδ T cells derived from lymphatic ducts draining the gut mucosa in Salmonella serovar Typhimurium infected calves were analyzed. In calves with enterocolitis, general gene expression trends in γδ T cells suggested subtle activation and innate response, whereas αβ T cells were relatively quiescent following Salmonella serovar Typhimurium infection. An increase in IL-2Rα expression on γδ T cells from infected calves and results from in vitro assays suggested that γδ T cells were primed by Salmonella serovar Typhimurium LPS to better respond to IL-2 and IL-15. Together with gene expression trends in vivo, these data support early priming activation of target tissue γδ T cells during Salmonella serovar Typhimurium infection.

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Stimulation of Human γδ T Cells by Nonpeptidic Mycobacterial Ligands

Cited by 660 publications

References 23 publications

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

Mucosal lymphatic-derived γδ T cells respond early to experimental Salmonella enterocolitis by increasing expression of IL-2Rα

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