γδ T-APCs: a novel tool for immunotherapy?

Moser, Bernhard; Eberl, Matthias

doi:10.1007/s00018-011-0706-6

Cited by 72 publications

(48 citation statements)

References 70 publications

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“…29 Both classic MHC I and MHC II loading pathways are therefore present in gd T cells. 30 Even though gd T cells predominantly exert innate-like responses, they are able to transform into memory cells. Thus na€ ıve (CD45RA C CD27 C ) and central memory (CD45RA ¡ CD27 C ) gd T cells will home to secondary lymphoid organs, while effector memory (CD45RA ¡ CD27 ¡ ) and terminally differentiated (CD45RA C CD27 ¡ ) gd T cells show immediate effector functions on inflammatory sites.…”

Section: Gd T Cells and Cancer Immunitymentioning

confidence: 99%

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Anguille

et al. 2015

OncoImmunology

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These authors equally contributed to the work.Keywords: gd T cell, cancer, DC-mediated gd T cell activation, dendritic cell, immunotherapy Abbreviations: gd, gamma delta; BCG, Bacillus Calmette-Guerin; BrHPP, bromohydrin pyrophosphate; CTL, cytotoxic T lymphocyte; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; HIV, human immunodeficiency virus; HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; iDC, immature DC; IFN, interferon; IL, interleukin; IPP, isopentyl pyrophosphate; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; mo-DC, monocyte-derived dendritic cell; pDC, plasmacytoid dendritic cell; PD, programmed cell death protein; TCR, T-cell receptor; Th, T-helper cell; TLR, toll-like receptor; TNF, tumor necrosis factor; Treg, regulatory T cellGamma delta (gd) T cells are the all-rounders of our immune-system with their major histocompatibility complexunrestricted cytotoxicity, capacity to secrete immunostimulatory cytokines and ability to promote the generation of tumor antigen-specific CD8 C and CD4 C T cell responses. Dendritic cell (DC)-based vaccine therapy has the prospective to harness these unique features of the gd T cells in the fight against cancer. In this review, we will discuss our current knowledge on DC-mediated gd T cell activation and related opportunities for tumor immunologists.

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Section: Gd T Cells and Cancer Immunitymentioning

confidence: 99%

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Anguille

et al. 2015

OncoImmunology

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“…While such a role can only be postulated in humans and at best supported by indirect epidemiological evidence, infection and/or vaccination experiments in non-human primates might address the contribution of Vg9/Vd2 T cells to the generation of high-affinity, class-switched antibodies. Such studies could exploit the availability of convenient pathogen models such as specially engineered HMB-PP-deficient strains of Listeria monocytogenes [45] or HMB-PP overproducing strains of Mycobacterium tuberculosis [46].Recent findings also point towards a more antigen-restricted role of Vg9/Vd2 T cells in providing B-cell help, given their potential to take up exogenous antigens and present them to CD4 1 and CD8 1 T cells [33,47]. Antigen-presenting gd T cells may thus be able to interact directly with T FH cells.…”

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confidence: 99%

“…Recent findings also point towards a more antigen-restricted role of Vg9/Vd2 T cells in providing B-cell help, given their potential to take up exogenous antigens and present them to CD4 1 and CD8 1 T cells [33,47]. Antigen-presenting gd T cells may thus be able to interact directly with T FH cells.…”

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confidence: 99%

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

et al. 2011

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Vc9/Vd2 T cells are a minor subset of T cells in human blood and differ from all other lymphocytes by their specific responsiveness to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a metabolite produced by a large range of microbial pathogens. Vc9/Vd2 T cells can be skewed towards distinct effector functions, in analogy to, and beyond, the emerging plasticity of CD4 1 T cells. As such, depending on the microenvironment, Vc9/Vd2 T cells can assume features reminiscent of Th1, Th2, Th17 and Treg cells as well as professional APCs. We here demonstrate that Vc9/Vd2 T cells express markers associated with follicular B helper T (T FH ) cells when stimulated with HMB-PP in the presence of IL-21. HMB-PP induces upregulation of IL-21R on Vc9/Vd2 T cells. In return, IL-21 plays a co-stimulatory role in the expression of the B-cell-attracting chemokine CXCL13, the CXCL13 receptor CXCR5 and the inducible co-stimulator by activated Vc9/Vd2 T cells, and enhances their potential to support antibody production by B cells. The interaction between HMB-PP-responsive Vc9/Vd2 T cells, IL-21-producing T FH cells and B cells in secondary lymphoid tissues is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections. Key words: Bacterial infections . B cells . cd T cells . IL-21 . T FH cells IntroductionThe establishment of long-term humoral immunity depends on the production of high-affinity antibodies capable of neutralising and opsonising invading pathogens. These antibodies are generated through somatic hypermutation, class switch recombination and affinity maturation of activated B cells, processes that take place in the germinal centres (GCs) of secondary lymphoid organs and depend on cognate help provided by CD4 1 follicular B helper T (T FH ) cells [1,2]. Human T FH cells are defined by the expression of characteristic markers [3][4][5][6][7]: the transcriptional repressor Bcl-6 that directs T FH lineage commitment; the chemokine receptor CXCR5 that enables T FH cells to migrate into the B-cell follicles; the CXCR5 ligand CXCL13 that attracts further CXCR5 1 cells such as naïve B cells and early activated CD4 1 T cells; the co-stimulatory molecules, inducible co-stimulator (ICOS) and programmed cell death 1 (PD-1), which interact with their corresponding ligands on B cells; and the cytokine IL-21 that steers B-cell differentiation and antibody production. Murine T FH cells express the same panel of markers with the exception of CXCL13.While the crucial role of T FH cells in providing B-cell help is undisputed, other T-cell subsets including CD8 1 T cells, NKT cells and gd T cells contribute to the outcome of humoral immune responses [8][9][10]. gd T cells support antibody production in immunised and infected mice [11][12][13] 110 [17,18], where they are scattered throughout the T zone and clustered within GCs [8]. Early studies in lupus patients led to the isolation of human gd T-cell lines capable of inducing autoantibody production by autologous B cells [19]. Subsequent ...

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“…In addition to their direct anti-infection activities, human cd-T cells act as professional APCs and take up, process and present pathogen-related antigens from both free viral particles 29 and infected cells 57,105 to other effector immune cells. 106,107 These cd-T APCs express approximately similar levels of HLA-DR and CD80/ CD86 compared to traditional APCs 29 and induce NK cell activation, 108,109 antigen-specific ab-T-cell responses 29,107 and even antibody production. 67 Although the physiological roles of cd-T APCs still need to be illuminated by more in vivo studies, recent investigations of murine cd-T cells have confirmed the general existence of cd-T APCs.…”

Section: Direct Anti-infection Activity Mediated By Cd-t Cells Directmentioning

confidence: 99%

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

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cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

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γδ T-APCs: a novel tool for immunotherapy?

Cited by 72 publications

References 70 publications

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

IL‐21 enhances the potential of human γδ T cells to provide B‐cell help

γδ-T cells: an unpolished sword in human anti-infection immunity

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