Vδ1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1–infected patients and respond to Candida albicans

Fenoglio, Daniela; Poggi, Alessandro; Catellani, Silvia; Battaglia, Florinda; Ferrera, Alessandra; Setti, Maurizio; Murdaca, Giuseppe; Zocchi, Maria Raffaella

doi:10.1182/blood-2009-01-198028

Cited by 152 publications

(150 citation statements)

References 51 publications

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“…8 Of note, Vc9Vd2 T cells are not the only human T-cell subset capable of producing IL-17; Vd1 T cells also can produce IL-17 specifically in the context of HIV-1 infection, in which they are markedly expanded. 29 In our experimental system, 8 antigen-stimulated cd17 T cells produce neither IL-22 nor IFN-c, in contrast with studies by Morita and colleagues, 7 which show that cd17 T cells also produce IL-22 and/or IFN-c. This finding is consistent with the concept that although they retain the memory of the imprinted cytokine, polarized T cells may undergo further differentiation in response to polarizing cues.…”

Section: Introductioncontrasting

confidence: 52%

Mechanisms underlying lineage commitment and plasticity of human γδ T cells

et al. 2012

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Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, cd T cells differentiate into two major types of memory T cells: central memory cells, which patrol the blood and secondary lymphoid organs, and effector memory cells, which migrate to peripheral tissues. cd T cells display in vitro a certain degree of plasticity in their function that is reminiscent of that which is observed in conventional CD4 T cells. Similar to CD4 T cells, in which a plethora of specialized subsets affect the host response, cd T cells may readily and rapidly assume distinct Th1-, Th2-, Th17-, T FH and T regulatory-like effector functions, suggesting that they profoundly influence cell-mediated and humoral immune responses. In addition to differences in cytokine repertoire, cd T cells exhibit diversity in homing, such as migration to lymph node follicles, to help B cells versus migration to inflamed tissues. Here, we review our current understanding of cd T-cell lineage heterogeneity and flexibility, with an emphasis on the human system, and propose a classification of effector cd T cells based on distinct functional phenotypes.

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Section: Introductioncontrasting

confidence: 52%

Mechanisms underlying lineage commitment and plasticity of human γδ T cells

et al. 2012

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“…Non-CD1-restricted Vd1 + T cells recognize and kill a variety of tumor cells [206][207][208] and cells infected with CMV [209,210] and HIV [211,212], and release cytokines in response to bacteria and fungi [213,214]. Once activated, Vd1 + T cells can drive DC maturation [215] but also kill DCs [216].…”

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

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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“…Vd1 cells also regulate the immune response 8,9 in addition to exerting anti-tumor [10][11][12][13][14] and anti-viral effects. [15][16][17] For example, a dominant Vd1 T-cell population in tumor-infiltrating lymphocytes triggers potent immunosuppression via toll-like receptor 8 signaling. 18 Therefore, the ratio of Vd1 to Vd2 T cells increases in the peripheral blood of tolerant recipients after liver transplantation and in cases of accepted grafts.…”

Section: Introductionmentioning

confidence: 99%

A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

et al. 2015

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Interleukin 4 (IL-4) has a variety of immune functions, including helper T-cell (Th-cell) differentiation and innate immune-response processes. However, the impact of IL-4 on gamma delta (cd) T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of cd T cells and the balance between variable delta 1 (Vd1) and Vd2 T cells in humans. The results show that IL-4 inhibits the activation of cd T cells in the presence of cd T-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated cd T cells and increased the levels of Vd1 T cells, which in turn inhibited Vd2 T-cell growth via significant IL-10 secretion. Vd1 T cells secreted significantly less interferon gamma (IFNc) and more IL-10 relative to Vd2. Furthermore, Vd1 T cells showed relatively low levels of Natural Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that Vd1 T cells weaken the cd T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in cd T cell-mediated anti-tumor immunity. Cellular & Molecular Immunology

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Vδ1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1–infected patients and respond to Candida albicans

Cited by 152 publications

References 51 publications

Mechanisms underlying lineage commitment and plasticity of human γδ T cells

Mechanisms underlying lineage commitment and plasticity of human γδ T cells

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

A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

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