Invariant NKT cells sustain specific B cell responses and memory

Galli, Grazia; Pittoni, Paola; Tonti, Elena; Malzone, Carmine; Uematsu, Yasushi; Tortoli, Marco; Maione, Domenico; Volpini, Gianfranco; Finco, Oretta; Nuti, Sandra; Tavarini, Silvia; Dellabona, Paolo; Rappuoli, Rino; Abrignani, Sergio

doi:10.1073/pnas.0700191104

Cited by 216 publications

(228 citation statements)

References 52 publications

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“…Coadministration of a-GC with immunizing antigen to mice results in enhanced production of antibodies specific for the antigen [170][171][172], demonstrating that the adjuvant effect of iNKT cells is antigen-specific. This help provided by iNKT cells results in the induction of long-lived antibody-secreting plasma cells, affinity maturation and the generation of memory B cells [172][173][174][175]. iNKT cells can also provide help for B cells specific for lipid-containing antigens internalized through the B cell receptor [176,177].…”

Section: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 97%

“…In murine models, CD1d and iNKT cells are required for the generation of protective antibody responses against microbial pathogens [167][168][169]. Coadministration of a-GC with immunizing antigen to mice results in enhanced production of antibodies specific for the antigen [170][171][172], demonstrating that the adjuvant effect of iNKT cells is antigen-specific. This help provided by iNKT cells results in the induction of long-lived antibody-secreting plasma cells, affinity maturation and the generation of memory B cells [172][173][174][175].…”

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

“…Marginal zone B cells are the most efficient B cell subset at presenting glycolipids to iNKT cells [177], which frequently possess a T FH -like phenotype (CXCR5 + , PD-1 + , CD28 + , IL-21 + ) [178]. Crosstalk between the two cell types involves CD40/CD40L interactions but does not appear to depend on IFN-c or IL-4 [172]. The contribution of human iNKT cells to B cell help was first reported by Galli et al [179], who co-cultured expanded CD4 + and CD4 À iNKT cell lines with B cells in vitro and found that both subsets induced B cell proliferation and antibody production.…”

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

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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: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 97%

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

Section: Other Unconventional T Cells Bridging Innate and Adaptive Immentioning

confidence: 99%

See 1 more Smart Citation

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

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…Stimulation by both IL-4 and IL-13 was also required for iNKT-cell-derived B-cell help, whereas CD40L-CD40 interactions were only partially involved in these responses [32]. Accordingly, the T H 0 CD4 + iNKT-cell subset was markedly more efficient than the T H 1 CD4 − iNKT-cell subset in providing B-cell help [32].Subsequent studies demonstrated that immunization of mice with αGalCer along with protein or hapten-carrier Ags elicits high titers of Ag-specific, class-switched Abs [33][34][35], significantly enhancing features of the Ab response in vivo, such as protection from infections [33,35] and long-lasting B-cell memory [35]. The adjuvant effect of αGalCer was comparable to that of benchmark adjuvants that are being utilized for human vaccination [35] and was independent of the route of administration [35].…”

mentioning

confidence: 99%

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

2014

Self Cite

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T-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4 + T follicular helper (T FH ) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations.Keywords: B-cell help r CD1d r T follicular helper cells r vaccines IntroductionThe production of neutralizing antibodies (Abs) by B cells represents a major parameter of host defense against infectious pathogens and is a key component of protective immune responses elicited by vaccines [1]. The innate and adaptive arms of the immune system are functionally separated, but seem to be highly coordinated to ensure an optimal outcome of immune responses. Although innate and adaptive immune cells are endowed with very distinct functions and timing of response, there are specialized lymphocyte subsets that straddle the two programs, and these cells have been defined as innate-like lymphocytes [2]. CD1d-rectricted invariant Vα14 natural killer T (iNKT) cells are one of the best characterized types of innate-like T lymphocytes, which display multiple effector functions upon activation [3]. Here, we review the mechanisms through which iNKT cells help B cells to promote Ab production and memory formation.Correspondence: Dr. Paolo Dellabona e-mail: dellabona.paolo@hsr.itThe TD and TI paradigm of the B-cell response B-cell responses are generally described as T-dependent (TD) or T-independent (TI), based on the requirement for T-cell help for Ab production. TD responses are induced by protein antigens (Ags) that are recognized by specific B cells in the presence of cognate T-cell help, which is provided by a specialized subset of CD4 + T helper (Th) cells called T follicular helper (T FH ) cells [4]. Ags reach the follicles, the B-cell zone of secondary lymphoid organs, and activate B cells upon binding to the specific B-cell receptors (BCRs [5]). This leads to Ag internalization, presentation of the processed Ag peptides into MHC class II (MHC II) molecules, and migration of the activated B cells to the border of the T-B-cell zone [4]. T FH cells are induced in the T-cell zone by dendritic cells (DCs) t...

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“…It suggests that NKT cells can influence immune responses by the regulation of chemokines expression, which is likely to shape the ensuing immune responses [73,74] . In addition, NKT cells can enhance antigen specific B cell response to secrete elevated levels of IgG, which leads to antibodydependent cellular cytotoxity (ADCC) to lyse cancer cells mediated by NK cells [75] . Moreover, NKT cells facilitate proper www.nature.com/aps Tan JQ et al Acta Pharmacologica Sinica npg DCs maturation and also improve migration of more mature DCs towards tumor sites from lymph nodes [76,77] .…”

Section: Nkt Cells In Tumor Immunitymentioning

confidence: 99%

Type I natural killer T cells: naturally born for fighting

et al. 2010

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Type І natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Vαβ TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type І NKT cells may play a critical role in modulating the upcoming immune responses, such as anti-tumor response, protection against infection, and autoimmunity. As a bridge between innate and adaptive immunity, type І NKT cells differentiate and mature upon stimulations to achieve and maintain a homeostasis. Orchestrating with other arms of adaptive immunity, type І NKT cells show strong cytotoxic effects in response to various tumors in a direct and/or indirect manner(s). This review will focus primarily on type І NKT cell development, homeostasis, and effector functions, especially in anti-tumor immunity, and followed by their potential applications in treatment of cancers.

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Invariant NKT cells sustain specific B cell responses and memory

Cited by 216 publications

References 52 publications

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

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

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

Type I natural killer T cells: naturally born for fighting

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