Natural killer T cell anergy, co-stimulatory molecules and immunotherapeutic interventions

Singh, Avadhesh Kumar; Gaur, Poonam; Das, Srinibas

doi:10.1016/j.humimm.2013.12.004

Cited by 35 publications

(33 citation statements)

References 94 publications

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“…It is thus of interest to determine whether the α-C-GC modified BCG vaccine vector induces NKT cell anergy when given by a standard vaccination route (i.e., subcutaneously), which might have undesirable effects on post-vaccination immune status. Induction of anergy in NKT cells following systemic stimulation with α-GC has been correlated with increased surface expression of PD-1 [29]. Therefore, we analyzed PD-1 expression on the surface of CD1d/α-GC tetramer positive NKT cells in the spleens of mice following s.c. administration of 5×10 6 CFU of α-C-GC modified rBCG-SIV gag .…”

Section: Resultsmentioning

confidence: 99%

Improving Mycobacterium bovis Bacillus Calmette-Guèrin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells

Venkataswamy

Kharkwal

et al. 2014

PLoS ONE

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Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

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Section: Resultsmentioning

confidence: 99%

Improving Mycobacterium bovis Bacillus Calmette-Guèrin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells

Venkataswamy

Kharkwal

et al. 2014

PLoS ONE

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“…Due to its potent agonistic activity, aGalCer has been tested in clinical trials for the treatment of tumor patients (Fujii et al 2013). Despite limiting success with free aGalCer itself, novel aGalCer analogs that are more potent for human iNKT cells, and different delivery routes, are under continuing development as therapeutic agents (Fujii et al 2013;Singh et al 2014).…”

Section: The Characterization Of Inkt Cell Antigensmentioning

confidence: 99%

From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

Wingender

2015

Arch. Immunol. Ther. Exp.

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Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined.

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“…Esta coestimulación de iNKT con 4-1BB/4-1BBL aumenta la secreción de IFN-γ, la proliferación celular, la expresión de CD25 y la respuesta a IL-2 (figura 1) (45). Entre las moléculas coestimuladoras más importantes que llevan a la producción de citocinas Th2 están OX40-OX40L (OX40 es el CD134) y TIM (receptores de células T con dominios de mucina e inmunoglobulina) (45). La expresión de OX40L en las iNKT define la respuesta de citocinas tipo Th2 y los niveles de IgE.…”

Section: Señales Coestimuladoras En La Polarización De Las Inktunclassified

Mecanismos de activación de las células T asesinas naturales invariantes (iNKT)

Baena

Gómez-Giraldo

Carreño

2015

iatreia

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RESUMENAunque se ha logrado un conocimiento amplio acerca de las células T asesinas naturales (iNKT), aún no existe consenso sobre sus mecanismos de activación. Dichas células reconocen diferentes antígenos glicolipídicos presentados por medio de la molécula CD1d, los cuales pueden ser endógenos, exógenos derivados de organismos como bacterias y sintéticos desarrollados para aplicaciones clínicas. Existe mucho interés en entender cómo estas distintas variantes glicolipídicas inducen diferentes tipos de polarización, pero ha sido muy difícil llegar a un consenso, debido a que la respuesta depende de varios factores como la naturaleza, la internalización y el procesamiento de los glicolípidos. Además, la activación de las células iNKT la determinan el tipo y estado de activación de la célula presentadora de antígeno, las moléculas coestimuladoras, los mecanismos de transactivación y la localización de los complejos CD1d-glicolípido en distintas microrregiones de la membrana plasmática, como las balsas lipídicas. Esta revisión explora la evidencia sobre los factores que afectan la activación de las células iNKT con el fin de entender su potencial inmunomodulador. PALABRAS CLAVEα-Galactosilceramida; Células Inkt; CD1d; Glicolípidos; Presentación Antigénica; TCR SUMMARY Activation mechanisms of invariant natural killer T cells (iNKTs)A great amount of knowledge on natural killer T cells (iNKTs) is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from

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Natural killer T cell anergy, co-stimulatory molecules and immunotherapeutic interventions

Cited by 35 publications

References 94 publications

Improving Mycobacterium bovis Bacillus Calmette-Guèrin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells

Improving Mycobacterium bovis Bacillus Calmette-Guèrin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells

From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

Mecanismos de activación de las células T asesinas naturales invariantes (iNKT)

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