Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

O’Reilly, Vincent; Zeng, Shijuan Grace; Bricard, Gabriel; Atzberger, Ann; Hogan, Andrew E.; Jackson, J. F.; Feighery, Conleth; Porcelli, Steven A.; Doherty, Derek G.

doi:10.1371/journal.pone.0028648

Cited by 90 publications

(115 citation statements)

References 62 publications

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“…Mock-transfected or CD1d-transfected HeLa cells were pulsed for 18-24 hours with medium alone or with 0.1, 1 or 10 µg/mL of glycolipid antigen. 13,19 Equal numbers of expanded and rested NKT cells were added for a further 24 hours and cell supernatants were then harvested and assayed for the T H 1, T H 2 and regulatory cytokines IFN-γ, IL-4 and IL-10, Compound 1 or Compound 2 at 0.1, 1 and 10 µg/mL (increasing concentrations denoted by triangles). After 24 hours equal numbers of expanded human NKT cells were added.…”

Section: Resultsmentioning

confidence: 99%

“…A 1M solution of triphenylphosphine in THF (1 mL, 1.0 mmol) was added dropwise to a solution of compound 17 (159 mg, 0.19 mmol) in THF (6 mL) at room temperature. After stirring for 2 h, 1M aqueous NaOH (3 mL) was added and the reaction was left to stir for a further 2 h. The solution was then diluted with EtOAc (15 mL) and washed with water (10 mL) and brine (10 mL 4, 128.35, 128.30, 128.2, 128.15, 127.85, 127.80 127.68, 127.55, 127.4, 126.9, 125.5 9, 31.5, 29.7, 29.65, 29.6, 29.55, 29.53, 29.50, 29.45, 29.36, 29.35, 29.34, 29.33, 29.28, 28.9 (19). A 1M solution of triphenylphosphine in THF (0.21 mL, 0.21 mmol) was added dropwise to a solution of compound 17 (38 mg, 0.04 mmol) in THF (1.5 mL) at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and immunostimulatory activity of two α-S-galactosyl phenyl-capped ceramides

Petrasca¹,

Murphy²,

O’Reilly³

et al. 2013

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis and immunostimulatory activity of two α-S-galactosyl phenyl-capped ceramides

Petrasca¹,

Murphy²,

O’Reilly³

et al. 2013

Arkivoc

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“…29 Trends towards a greater proportion of CD4 + , and a lower proportion of CD8 + , iNKT cells were observed in patients with CLL, although these did not reach statistical significance ( Figure 1C). In both patients and controls, the proportion of CD4 …”

Section: Invariant Natural Killer T Cells In Cll Haematologica | 2013mentioning

confidence: 89%

Functional invariant natural killer T-cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy

et al. 2012

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ABSTRACTactive malignancy or previous chemotherapy for a disease other than CLL. All donors gave written informed consent. Ethical approval for the study was obtained from the Central Regional Ethics Committee of New Zealand.Binet and Rai prognostic scores were determined from the clinical examination and absolute differential blood counts (Sysmex XE 2100 analyzer, Roche Diagnostics, Auckland, New Zealand) measured at the time of blood sampling. Details of peripheral blood mononuclear cell (PBMC) isolation and storage, and B-cell depletion and enrichment are given in the Online Supplementary Design and Methods.

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“…Upon activation with a-GC in vitro, iNKT cells can kill target cells and secrete a diverse range of growth factors and cytokines [144][145][146]. Murine and human iNKT cells are unique in their ability to produce Th1 (IFN-c, TNF-a), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17A, IL-22) and regulatory T cell (IL-10) cytokines, at times simultaneously [152][153][154][155]. Cytokines released by iNKT cells contribute to the activation of T cells [156], NK cells [156,157], macrophages [158] and suppression of functions of neutrophils and myeloid-derived suppressor cells [159,160].…”

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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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Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

Cited by 90 publications

References 62 publications

Synthesis and immunostimulatory activity of two α-S-galactosyl phenyl-capped ceramides

Synthesis and immunostimulatory activity of two α-S-galactosyl phenyl-capped ceramides

Functional invariant natural killer T-cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy

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

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