CD1d-Restricted Immunoglobulin G Formation to GPI-Anchored Antigens Mediated by NKT Cells

Schofield, Louis; McConville, Malcolm J.; Hansen, Diana S.; Campbell, Stewart; Fraser‐Reid, Bert; Grusby, Michael J.; Tachado, Souvenir D.

doi:10.1126/science.283.5399.225

Cited by 358 publications

(262 citation statements)

References 34 publications

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“…The advantage of the model is that mice lack the aberrant T cell population that is found in MHC class II Ϫ/Ϫ mice and CD4 Ϫ/Ϫ mice. MHC class II Ϫ/Ϫ mice have residual CD1-restricted CD4 population (15,29), and CD4 Ϫ/Ϫ mice have increased numbers of an abnormal population of CD4 Ϫ CD8 Ϫ TCR␣␤ ϩ cells (13,30,31). CD8 cells in CD4 Ϫ/Ϫ mice can also be MHC class II restricted (32).…”

Section: Discussionmentioning

confidence: 99%

CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation

Zhan

Corbett

Brady

et al. 2000

The Journal of Immunology

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Mice made transgenic (Tg) for a rat anti-mouse CD4 Ab (GK mice) represent a novel CD4-deficient model. They not only lack canonical CD4 cells in the periphery, but also lack the residual aberrant Th cells that are found in CD4−/− mice and MHC class II−/− mice. To analyze the role of CD4 help and costimulation for CTL induction against alloantigens, we have assessed the surface and functional phenotype of CD8 cells in vivo (e.g., clearance of allogeneic P815 cells) and in vitro. In our CD4-deficient GK mice, CTL responses to allogeneic P815 cells were induced, albeit delayed, and were sufficient to eliminate P815 cells. Induction of CTL and elimination of allogeneic P815 cells were inhibited both in the presence and absence of CD4 cells by temporary CD40 ligand blockade. This indicated that direct interaction of CD40/CD40L between APCs and CD8 cells may be an accessory signal in CTL induction (as well as the indirect pathway via APC/CD4 interaction). Furthermore, whereas in CTLA4Ig single Tg mice P815 cells were rejected promptly, in the double Tg GK/CTLA4Ig mice CTL were not induced and allogeneic P815 cells were not rejected. These findings suggest that CD40/CD40L is involved in both CD4-dependent and CD4-independent pathways, and that B7/CD28 is pivotal in the CD4-independent pathway of CTL induction against allogeneic P815 cells.

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Section: Discussionmentioning

confidence: 99%

CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation

Zhan

Corbett

Brady

et al. 2000

The Journal of Immunology

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“…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.…”

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

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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“…Indeed, it is the ability of Ag-activated NKT cells to lyse tumor targets that has prompted clinical investigations into the use of ␣GalCer as an antitumor agent (16). By the study of mouse models of infection, CD1d and NKT cells have been implicated in host defense against a number of pathogens including Borrelia burgdorferi, Plasmodium species, and Mycobacterium tuberculosis (17)(18)(19).…”

mentioning

confidence: 99%

Human NKT Cells Express Granulysin and Exhibit Antimycobacterial Activity

Gansert

Kieβler

Engele

et al. 2003

The Journal of Immunology

165

139

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Human NKT cells are a unique subset of T cells that express an invariant Vα24 TCR that recognizes the nonclassical Ag-presenting molecule CD1d. Activation of NKT cells is greatly augmented by the marine sponge-derived glycolipid α-galactosylceramide (αGalCer). Because human monocyte-derived cells express CD1d and can harbor the intracellular pathogen Mycobacterium tuberculosis, we asked whether the addition of αGalCer could be used to induce effector functions of NKT cells against infected monocytes, macrophages, and monocyte-derived dendritic cells. NKT cells secreted IFN-γ, proliferated, and exerted lytic activity in response to αGalCer-pulsed monocyte-derived cells. Importantly, αGalCer-activated NKT cells restricted the growth of intracellular M. tuberculosis in a CD1d-dependent manner. NKT cells that exhibited antimycobacterial activity also expressed granulysin, an antimicrobial peptide shown to mediate an antimycobacterial activity through perturbation of the mycobacterial surface. Degranulation of NKT cells resulted in depletion of granulysin and abrogation of antimycobacterial activity. The detection of CD1d in granulomas of tuberculosis patients supports the potential interaction of NKT cells with CD1d-expressing cells at the site of disease activity. These studies provide evidence that αGalCer-activated CD1d-restricted T cells can participate in human host defense against M. tuberculosis infection.

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CD1d-Restricted Immunoglobulin G Formation to GPI-Anchored Antigens Mediated by NKT Cells

Cited by 358 publications

References 34 publications

CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation

CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation

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

Human NKT Cells Express Granulysin and Exhibit Antimycobacterial Activity

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