Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy

Laubert, Miriam; Bonifacius, Agnes; Dragon, Anna Christina; Mangare, Caroline; Blasczyk, Rainer; Huehn, Jochen

doi:10.3390/biology11040536

Cited by 4 publications

(3 citation statements)

References 47 publications

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“…The antioxidant property of vitamin C also relies on the reduction of ROS-mediated expression of proinflammatory cytokines including interleukin (IL)- 1 and tumor necrosis factor alpha (TNFα) by inhibiting nuclear factor kappa B (NF-kB) transcription [ 25 ]. The impact of ascorbic acid on T cells has also been verified through reports, suggesting that it strengthens antioxidant-mediated immunity and enhances the antigen-specific response of T cells, indicating the potential of vitamin C for altering immune responses [ 26 , 27 ]. Notably, a suboptimal reduction in antioxidants can impair immunosuppression by inducing T cell apoptosis.…”

Section: Overview On Impact Of Vitamin C On Innate and Adaptive Immun...mentioning

confidence: 98%

Impact of vitamin C on the development, differentiation and functional properties of T cells

Sasidharan Nair,

Huehn

2024

EuJMI

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Vitamin C plays a multifaceted role in various biological processes and is well-known to facilitate pleiotropic activities in both innate and adaptive immune responses, where the antioxidant capacity of vitamin C is most likely highly relevant since immune responses mainly occur in reducing environments. Beyond its antioxidant properties, vitamin C can enhance the transcription potential of genes by promoting DNA demethylation through ten-eleven-translocation (Tet) methylcytosine dioxygenases, which have been recently demonstrated to be critical for the development and differentiation of T cells. In this minireview, we will provide a broader overview on the impact of vitamin C on signaling and regulatory activities in both innate and adaptive immune cells. Particularly, we will summarize recent findings on the decisive role of finely tuned vitamin C concentrations for T cell development, T helper cell differentiation, and optimal T cell-mediated immune responses.

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Section: Overview On Impact Of Vitamin C On Innate and Adaptive Immun...mentioning

confidence: 98%

Impact of vitamin C on the development, differentiation and functional properties of T cells

Sasidharan Nair,

Huehn

2024

EuJMI

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“…Spermidine supplementation in hepatitis B virus (HBV)-vaccinated mice also improves Ag-specific CD8 T-cell protection [ 134 ]. Similarly, another recent study showed that cytomegalovirus (CMV)-specific T-cell functionality can be improved by vitamin C pre-treatment for several days [ 135 ]. Altogether, data show that while many approaches to stimulate autophagy with drugs and/or dietary supplementations, such as rapamycin, spermidine, niacin, and metformin, have shown promise in preclinical studies, their translation to HIV-1-related clinical application and their overall efficacy and safety profiles in PLWH require further investigations.…”

Section: Therapeutic Tools To Induce Autophagy In T-cells Of Plwhmentioning

confidence: 99%

Harnessing Autophagy to Overcome Antigen-Specific T-Cell Dysfunction: Implication for People Living with HIV-1

Ghahari,

Telittchenko,

Loucif

et al. 2023

IJMS

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Like other chronic viral infections, HIV-1 persistence inhibits the development of antigen-specific memory T-cells, resulting in the exhaustion of the immune response and chronic inflammation. Autophagy is a major lysosome-dependent mechanism of intracellular large-target degradation such as lipid and protein aggregates, damaged organelles, and intracellular pathogens. Although it is known that autophagy may target HIV-1 for elimination, knowledge of its function as a metabolic contributor in such viral infection is only in its infancy. Recent data show that elite controllers (EC), who are HIV-1-infected subjects with natural and long-term antigen (Ag)-specific T-cell protection against the virus, are characterized by distinct metabolic autophagy-dependent features in their T-cells compared to other people living with HIV-1 (PLWH). Despite durable viral control with antiretroviral therapy (ART), HIV-1-specific immune dysfunction does not normalize in non-controller PLWH. Therefore, the hypothesis of inducing autophagy to strengthen their Ag-specific T-cell immunity against HIV-1 starts to be an enticing concept. The aim of this review is to critically analyze promises and potential limitations of pharmacological and dietary interventions to activate autophagy in an attempt to rescue Ag-specific T-cell protection among PLWH.

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“…In general, VitC was found to preferentially drive T cells into the Th1 differentiation pathway [37, 38]. However, VitC also enhances the growth and effector activity of cytomegalovirus‐specific human CD8 CTL [39]. These effects are likely due to the antioxidant and epigenetic activity of VitC.…”

Section: Introductionmentioning

confidence: 99%

Empowering γδ T‐cell functionality with vitamin C

Kabelitz,

Cierna,

Juraske

et al. 2024

Eur J Immunol

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Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma. Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells. γδ T cells have recently attracted great interest as effector cells for cell‐based cancer immunotherapy, due to their HLA‐independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off‐the‐shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy. Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells. We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies.

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Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy

Cited by 4 publications

References 47 publications

Impact of vitamin C on the development, differentiation and functional properties of T cells

Impact of vitamin C on the development, differentiation and functional properties of T cells

Harnessing Autophagy to Overcome Antigen-Specific T-Cell Dysfunction: Implication for People Living with HIV-1

Empowering γδ T‐cell functionality with vitamin C

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