Harnessing invariant NKT cells in vaccination strategies

Cerundolo, Vincenzo; Silk, Jonathan D.; Masri, S. Hajar; Salio, Mariolina

doi:10.1038/nri2451

Cited by 323 publications

(339 citation statements)

References 121 publications

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“…Even more, other unconventional T cell subsets may drive similar reactions, albeit in response to different stimuli and in different anatomical contexts, arguing for a general role of innate T cell subsets as natural adjuvants to promote protective immune responses. In analogy to the exploitation of iNKT cells in the clinic [193][194][195]223,224], approaches specifically targeting Vc9/Vd2 T cells may have a similar potential as vaccine adjuvant, to boost immune responses against pathogens and tumors and to modulate autoimmune responses.…”

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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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

View full text Add to dashboard Cite

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“…In contrast to other MHC classes, CD1d is essentially monomorphic and can bind to a large selection of self, non-self and synthetic antigens [25]. Both human and murine intestinal epithelial cells (IEC) express CD1d [26], and therefore are capable of activating iNKT cells in the intraepithelial and lamina propria (LP) compartments [27]. CD1d is also expressed on intestinal APCs and B cells.…”

Section: Inkt Cellsmentioning

confidence: 99%

“…More recently Lee et al [46] characterized circulating MAIT cells in a large sample of 133 healthy adults and reported high variability in circulating MAIT cell numbers across subjects (0.19-21.7%). Although no significant differences in numbers between males and females were found there was a significant decrease in MAIT cell numbers in elderly subjects (n = 45, ages 61-92) versus young subjects (n = 44, ages [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Section: Characteristics Of Mait Cellsmentioning

confidence: 99%

Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections

Abautret-Daly¹,

Davitt²,

Lavelle³

2014

Biochemical Pharmacology

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“…71 Similarly, other glycospingolipids, such as a-GalCer, have been shown to alter the DC-NKT cell cross talk or to affect other regulatory T cells (Tregs). 133,134 GC promotes regulatory T cells Recent studies have suggested that glycosphingolipids can promote Tregs. This effect can be mediated by DCs or by cross talk between NKT cells and Tregs.…”

Section: Gc As a Ligand For DC Cellsmentioning

confidence: 99%

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

2009

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Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with lowdose ERT and re-evaluating the use of ERT in asymptomatic patients.

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Harnessing invariant NKT cells in vaccination strategies

Cited by 323 publications

References 121 publications

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

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

Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

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