Vγ9Vδ2 T Cells Impair Intracellular Multiplication of<i>Brucella suis</i>in Autologous Monocytes Through Soluble Factor Release and Contact-Dependent Cytotoxic Effect

Ottonès, Florence; Dornand, Jacques; Naroeni, Aroem; Liautard, Jean‐Pierre; Favero, Jean

doi:10.4049/jimmunol.165.12.7133

Cited by 57 publications

(56 citation statements)

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“…Ottones et al [66] reported morphological changes of monocytes co-cultured together with activated Vc9/Vd2 T cells yet did not characterize those activated monocytes in more detail. Other studies showed an induction of CD40, high-mobility group box 1 protein (HMGB-1) and tissue factor (TF) by monocytes in PBMC cultures treated with IPP or zoledronate [67,68].…”

Section: Differentiation Of Monocytes: Local Generation Of Inflammatomentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Section: Differentiation Of Monocytes: Local Generation Of Inflammatomentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…Also, it is reported that bacillus Calmette-Guérin vaccine application can exhibit significantly beneficial effect in controlling the malignancy, in particular the bladder cancers (41,42). Because many microbes are indicated to produce and secrete nonpeptide Ags for human ␥␦ T cells such as alkyl pyrophosphates and alkyl amines (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55), it is tempting to speculate that these microbial nonpeptide Ags may contribute to the restriction of growth of incidental tumor cells via stimulation of ␥␦ T cells to proliferate and produce IFN-␥ as well as sensitization of the tumor cells for the ␥␦ T cell-mediated cytotoxicity. Our recent report suggested that ␥␦ T cells might provide innate immunity in patients with renal cell carcinomas, implicating a possible link between tumor immunity and urinary infections (56).…”

Section: Discussionmentioning

confidence: 99%

Targeting of Tumor Cells for Human γδ T Cells by Nonpeptide Antigens

Kato

Tanaka

Miyagawa

et al. 2001

The Journal of Immunology

140

131

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Human Vγ2/Vδ2+ γδ T cells respond to low molecular-mass nonpeptide Ags in a γδ TCR-dependent manner. Although requirements of Ag presentation have remained controversial, we have indicated that specific responses of the primary γδ T cells to pamidronate were dependent on monocytic adherent cells for Ag presentation. Here, we show that human tumor cells can efficiently present aminobisphosphonate and pyrophosphomonoester compounds to γδ T cells, inducing specific proliferation and IFN-γ production. γδ TCR dependency of the response to Ag-pulsed tumor cells was confirmed by using a Jurkat line transfected with a Vγ2/Vδ2 γδ TCR. Furthermore, γδ T cells exhibited markedly enhanced cytotoxicity against the Ag-pulsed tumor cells as compared with untreated tumor cells. Survey of a number of human tumor cell lines of different origins revealed that the majority of them became susceptible for γδ T cell-mediated cytotoxicity following the Ag pulsing except for breast cancer lines so far examined, while normal PHA blast cells remained resistant. The results not only imply a unique mode of nonpeptide Ag recognition by human γδ T cells but also may provide a novel strategic clue for immunotherapy of human malignancy.

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“…(E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate immunotherapeutics ͉ lung ͉ macaques ͉ immune regulation ͉ clonal expansion A ccumulating evidence suggests that human V␥2V␦2 (also called V␥9V␦2) T cells may play a role in mediating immunity against microbial pathogens (1)(2)(3)(4)(5)(6)(7)(8). V␥2V␦2 T cells constitute 60-95% of circulating human ␥␦ T cells and are unique in their ability to massively expand during various bacterial and protozoal infections (9).…”

Section: The Possibility That V␥2v␦2 T Effector Cells Can Confer Protmentioning

confidence: 99%