CD1-mediated γ/δ T Cell Maturation of Dendritic Cells

Leslie, David S.; Vincent, Michael S.; Spada, Fabio; Das, Hiranmoy; Sugita, Masahiko; Morita, Craig T.; Brenner, Michael B.

doi:10.1084/jem.20021515

Cited by 185 publications

(167 citation statements)

References 33 publications

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“…Our results are in concordance with previous reports showing modulation of DC activity by cells restricted by monomorphic nonclassical MHC class I-like molecules (15,16). In addition, DNA microarray analysis of human iNKT activated with anti-CD3 Abs has been reported to show cytokine and chemokine expression profiles consistent with the recruitment and maturation of DC (49).…”

Section: Discussionsupporting

confidence: 82%

“…In support of this hypothesis, it has been shown in mice that stimulation of iNKT cells can enhance DC-based immunization strategies (14). Also, recent studies have shown that human NKT cell clones restricted to the group I CD1 molecules CD1a, CD1b, and CD1c, and ␥␦ T cells restricted by CD1c can directly induce maturation of cultured DC in vitro (15,16). Therefore, a range of CD1-restricted cells may be poised, together with direct microbial stimuli, to integrate innate immune responses with appropriate adaptive responses.…”

mentioning

confidence: 65%

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NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

Hermans

Silk

Gileadi

et al. 2003

The Journal of Immunology

453

454

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Modification in the function of dendritic cells (DC), such as that achieved by microbial stimuli or T cell help, plays a critical role in determining the quality and size of adaptive responses to Ag. NKT cells bearing an invariant TCR (iNKT cells) restricted by nonpolymorphic CD1d molecules may constitute a readily available source of help for DC. We therefore examined T cell responses to i.v. injection of soluble Ag in the presence or the absence of iNKT cell stimulation with the CD1d-binding glycolipid α-galactosylceramide (α-GalCer). Considerably enhanced CD4+ and CD8+ T cell responses were observed when α-GalCer was administered at the same time as or close to OVA injection. This enhancement was dependent on the involvement of iNKT cells and CD1d molecules and required CD40 signaling. Studies in IFN-γR−/− mice indicated that IFN-γ was not required for the adjuvant effect of α-GalCer. Consistent with this result, enhanced T cell responses were observed using OCH, an analog of α-GalCer with a truncated sphingosine chain and a reduced capacity to induce IFN-γ. Splenic DC from α-GalCer-treated animals expressed high levels of costimulatory molecules, suggesting maturation in response to iNKT cell activation. Furthermore, studies with cultured DC indicated that potentiation of T cell responses required presentation of specific peptide and α-GalCer by the same DC, implying conditioning of DC by iNKT cells. The iNKT-enhanced T cell responses resisted challenge with OVA-expressing tumors, whereas responses induced in the absence of iNKT stimulation did not. Thus, iNKT cells exert a significant influence on the efficacy of immune responses to soluble Ag by modulating DC function.

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 65%

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

Hermans

Silk

Gileadi

et al. 2003

The Journal of Immunology

453

454

View full text Add to dashboard Cite

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“…The molecular nature of such factors is not known but Ruedl et al (12) and Muraille et al (8) have excluded CD28, CD40L, receptor activator of NF-B ligand, TNF, IL-1, IL-4, IL-6, IL-17, IFN␣␤, and IFN-␥. In contrast, human DC maturation induced by CD8 ϩ or ␥␦ T cells is largely mediated by IFN-␥ and/or TNF, respectively (13,38).…”

Section: Discussionmentioning

confidence: 99%

Newly Activated T Cells Promote Maturation of Bystander Dendritic Cells but Not IL-12 Production

Spörri

Sousa

2003

The Journal of Immunology

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The activation of dendritic cells (DC) leads to increased costimulatory activity (termed DC maturation) and, in some instances, production of immunomodulatory cytokines such as IL-12. Both innate and T cell-derived signals can promote DC activation but it is unclear to what extent the two classes of stimuli are interchangeable or regulate distinct aspects of DC function. In this study, we show that signals from newly activated CD4+ T cells cannot initiate IL-12 synthesis although they can amplify secretion of bioactive IL-12 p70 by DC exposed to an appropriate innate stimulus. This occurs exclusively in cis and does not influence IL-12 synthesis by bystander DC that do not present Ag. In marked contrast, signals from newly activated CD4+ T cells can induce an increase in DC costimulatory activity in the absence of any innate priming. This occurs both in cis and in trans, affecting all DC in the microenvironment, including those that do not bear specific Ag. Consistent with the latter, we show that newly activated CD4+ T cells in vivo can deliver “help” in trans, effectively lowering the number of MHC/peptide complexes required for proliferation of third-party naive CD4+ T cells recognizing Ag on bystander DC. These results demonstrate that DC maturation and cytokine production are regulated distinctly by innate stimuli vs signals from CD4+ T cells and reveal a process of trans activation of DC without secretion of polarizing cytokines that takes place during T cell priming and may be involved in amplifying immune responses.

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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%

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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CD1-mediated γ/δ T Cell Maturation of Dendritic Cells

Cited by 185 publications

References 33 publications

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

Newly Activated T Cells Promote Maturation of Bystander Dendritic Cells but Not IL-12 Production

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

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