Cutting Edge: CD1d Restriction and Th1/Th2/Th17 Cytokine Secretion by Human Vδ3 T Cells

Mangan, Bozgana A.; Dunne, Margaret R.; O’Reilly, Vincent; Dunne, Pádraic J.; Exley, Mark A.; O’Shea, Donal; Scotet, Emmanuel; Hogan, Andrew E.; Doherty, Derek G.

doi:10.4049/jimmunol.1300121

Cited by 136 publications

(140 citation statements)

References 25 publications

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“…We also confirm a previous report (17) that C. albicans drives expansion and IL-17 production by human Vd1 T cells in vitro. We initially tested several protocols (30,31) for expanding Vd1 T cells and found that coculturing PBMCs enriched for gd T cells with DCs activated with the dectin-1 ligand curdlan in the presence of PHA and IL-2 resulted in the selective expansion of Vd1 T cells. Subsequently, it was found that substituting curdlan with heat-or ethanol-inactivated C. albicans, also known to bind dectin-1 (18)(19)(20), could similarly promote Vd1 T cell expansion in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…A number of protocols for the ex vivo expansion of human gd T cells from healthy donors were tested (30,31), and the following method was optimized for generating lines of Vd1 T cells. PBMCs prepared from buffy coat packs were enriched for total gd T cells using Ab-coated magnetic beads and cultured for 7-14 d in medium containing PHA-L and IL-2, with monocyte-derived DCs that had been matured overnight with curdlan or heat-or ethanolkilled C. albicans ( Fig.…”

Section: Albicans Drives the Expansion Of Vd1 T Cells In Vitromentioning

confidence: 99%

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Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

Maher

Dunne

Comerford

et al. 2015

The Journal of Immunology

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γδ T cells expressing the Vδ1 TCR are expanded in patients with HIV infection. We show in this article that circulating Vδ1 T cell numbers are particularly high in patients with HIV and candidiasis, and that these cells expand and produce IL-17 in response to Candida albicans in vitro. Although C. albicans could directly stimulate IL-17 production by a subset of Vδ1 T cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans–responsive Vδ1 T cells to generate sufficient numbers of cells to release IL-17 at levels detectable by ELISA. C. albicans induced the release of IL-1β, IL-6, and IL-23 by DCs, but addition of these cytokines or supernatants of C. albicans–treated DCs to Vδ1 T cells was not sufficient to induce proliferation. We found that direct contact with DCs was required for Vδ1 T cell proliferation, whereas IL-23R–blocking studies showed that IL-23 was required for optimal C. albicans–induced IL-17 production. Because IL-17 affords protection against both HIV and C. albicans, and because Vδ1 T cells are not depleted by HIV, these cells are likely to be an important source of IL-17 in HIV-infected patients with candidiasis, in whom CD4+ Th17 responses are impaired. These data show that C. albicans stimulates proliferation and IL-17 production by Vδ1 T cells by a mechanism that involves IL-23 release by DCs.

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Section: Discussionmentioning

confidence: 99%

Section: Albicans Drives the Expansion Of Vd1 T Cells In Vitromentioning

confidence: 99%

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

Maher

Dunne

Comerford

et al. 2015

The Journal of Immunology

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“…Several studies have demonstrated CD1a, CD1b, CD1c and CD1d reactivity of human Vd1 + T cells [198][199][200][201][202][203] and CD1d-reactivity of human Vd3 + T cells [204]. Roles for CD1-restricted Vd1 + and Vd3 + T cells in the induction of adaptive immune responses are evident from studies that have shown that these cells can induce MHC and costimulatory receptor expression and cytokine production by DC, conferring upon DC the capacity to drive alloreactive T cell proliferation [204,205]. Additionally, one report described the ability of CD1-restricted Vd1 + T cells specific for pollen-derived phosphatidyl-ethanolamine to drive IgE production by B cells [200].…”

Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

“…Whilst Vc9/Vd2 T cells make up the majority of peripheral human cd T cells, Vd1 + and Vd3 + ('Vd2 neg ') T cells are the predominant cd T cell subtypes in human intestine and liver [196,197]. Several studies have demonstrated CD1a, CD1b, CD1c and CD1d reactivity of human Vd1 + T cells [198][199][200][201][202][203] and CD1d-reactivity of human Vd3 + T cells [204]. Roles for CD1-restricted Vd1 + and Vd3 + T cells in the induction of adaptive immune responses are evident from studies that have shown that these cells can induce MHC and costimulatory receptor expression and cytokine production by DC, conferring upon DC the capacity to drive alloreactive T cell proliferation [204,205].…”

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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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“…Vδ3 T cells are a minor population in the blood but are more dominant in the liver and in leukemic patients. Upon activation with IL-2, Vδ3 T cells are expanded and recognize CD1d and, thereby, can lyse CD1d + target cells and release cytokines such as IL-17 and IFN-γ (46). A substantial body of evidence now demonstrates that γδ T cells play a central role in defending the host against a wide range of infections as well as sterile stresses such as malignant transformation.…”

Section: γδ T Cells: Development Tissue Distribution and Functionmentioning

confidence: 99%

Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy

et al. 2016

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Excitement is growing for therapies that harness the power of patients’ immune systems to combat their diseases. One approach to immunotherapy involves engineering patients’ own T cells to express a chimeric antigen receptor (CAR), to treat advanced cancers, particularly those refractory to conventional therapeutic agents. Although these engineered immune cells have made remarkable strides in the treatment of patients with certain hematologic malignancies, success with solid tumors has been limited, probably due to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date, T cells bearing αβ receptors have been used to generate CAR T cells. In this review, we highlight biological characteristics of γδ T cells that are distinct from those of αβ T cells, including homing to epithelial and mucosal tissues and unique functions such as direct antigen recognition, lack of alloreactivity, and ability to present antigens. We offer our perspective that these features make γδ T cells promising for use in cellular therapy against several types of solid tumors, including melanoma and gastrointestinal cancers. Engineered γδ T cells should be considered as a new platform for adoptive T cell cancer therapy for mucosal tumors.

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Cutting Edge: CD1d Restriction and Th1/Th2/Th17 Cytokine Secretion by Human Vδ3 T Cells

Cited by 136 publications

References 25 publications

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

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

Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy

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