CXCR5 Identifies a Subset of Vγ9Vδ2 T Cells which Secrete IL-4 and IL-10 and Help B Cells for Antibody Production

Caccamo, Nadia; Battistini, Luca; Bonneville, Marc; Poccia, Fabrizio; Fournié, Jean Jacques; Meraviglia, Serena; Borsellino, Giovanna; Kroczek, Richard A.; Mendola, Carmela La; Scotet, Emmanuel; Dieli, Francesco; Salerno, Alfredo

doi:10.4049/jimmunol.177.8.5290

Cited by 138 publications

(164 citation statements)

References 40 publications

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“…Indeed, microarray studies revealed that Vc9/Vd2 T cells primed in the presence of IL-21 assume features typically associated with human T FH cells, most notably the expression of the B cell attracting chemokine, CXCL13, which is key in recruiting B cells to secondary lymphoid tissue and establishing germinal centers [74]. On a functional level, activated Vc9/Vd2 T cells readily provide B cell help in vitro, with a particular contribution of Vc9/Vd2 T cell-expressed CD40L and inducible T cell co-stimulator (ICOS) as well as IL-4 and IL-10 [111,112]. These findings identify an intimate tripartite crosstalk between antigenspecific CD4 + T FH cells, HMB-PP responsive Vc9/Vd2 T cells and follicular B cells in which both CD4 + and cd T cells regulate the recruitment of further cells to the germinal center and the production and affinity maturation of class-switched antibodies [113,114] (Fig.…”

Section: Provision Of B Cell Help: Boosting Humoral Immunitymentioning

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: Provision Of B Cell Help: Boosting Humoral Immunitymentioning

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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“…For example, the inducible costimulator-inducible costimulator ligand interaction has been found to arm cd-T cells with some of the properties of follicular T cells and thus assist in antibody production by B cells. 67 In addition to the conventional costimulators that are shared with ab-T cells, several novel molecules can serve as the secondary signals for the activation of cd-T cells. It has been found that the expression of junctional adhesion molecule-like protein 68 and high-mobility group box 1 69 by cd-T cells provides positive signals for the activation of cd-T cells, whereas stimulation with E-cadherin downregulates their functions.…”

Section: Host Cell-derived Signalsmentioning

confidence: 99%

“…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. 110 Modifying adaptive immunity.…”

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

confidence: 99%

“…111 The contribution of cd-T cells to adaptive immunity goes beyond their APC function mentioned above. For example, cd-T cells are capable of inducing the maturation of DCs, 67 facilitating the development of ab-T cells, 13,112 killing regulatory T cells (Tregs) 113,114 and migrating into the secondary lymphoid tissues and acting as follicular B helper T cells to promote antibody production. 115,116 Moreover, cd-T cells can compete with ab-T cells for growth factors such as IL-15 and thus modify the adaptive immune response.…”

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

confidence: 99%

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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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“…By analogy with terminally differentiated CD8 memory T cells (3), these gd T cells are present in inflammatory sites and were referred to as T effector memory helper 1 (TEMh1) and T effector memory RA (TEMRA), respectively (4,5). A fifth maturation stage of Vg9Vd2 T lymphocytes has been further identified on the basis of CXCR5 expression and was defined as follicular helper gd cells for its phenotypic and functional analogy with conventional follicular helper CD4 lymphocytes (6).…”

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confidence: 99%

Phosphoantigens Overcome Human TCRVγ9+ γδ Cell Immunosuppression by TGF-β: Relevance for Cancer Immunotherapy

Capietto

Martinet

Cendron

et al. 2010

The Journal of Immunology

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Human γδ cells expressing TCRVγ9 are HLA-unrestricted CTLs with high relevance for cancer immunotherapy. Many tumor cell types produce TGF-β, however, a cytokine strongly immunosuppressive for conventional T CD4, CD8, and NK cells. Whether TGF-β also inhibits TCRVγ9+ lymphocytes was unknown. Because phosphoantigens (PAgs), such as bromohydrin pyrophosphate, selectively activate the antitumor functions of TCRVγ9+ T cells, in this study, we investigated whether TGF-β modulates these functions. We report that TGF-β does not block activation of TCRVγ9+ T cells but inhibits their PAg/IL-2–induced proliferation and maturation into effector cells and finally reduces the cytotoxic activity of these γδ T cells when exposed to lymphoma target cells. TGF-β did not bias their differentiation pattern toward γδ Th17 or γδ regulatory T cells. Nevertheless, increasing doses of PAg stimulus countered TGF-β inhibition. So, although TGF-β impairs TCRVγ9+ γδ cells like other cytolytic lymphocytes, PAg alone or combined to therapeutic mAb has the ability to bypass its immunosuppressive activity.

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CXCR5 Identifies a Subset of Vγ9Vδ2 T Cells which Secrete IL-4 and IL-10 and Help B Cells for Antibody Production

Cited by 138 publications

References 40 publications

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

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

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

Phosphoantigens Overcome Human TCRVγ9+ γδ Cell Immunosuppression by TGF-β: Relevance for Cancer Immunotherapy

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