Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation

Horch, Matthew; Nguyen, Vu

doi:10.1177/2040620711422266

Cited by 7 publications

(8 citation statements)

References 109 publications

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“…Despite this new data, however, the effect of VitC on endogenous nTreg has been neglected thus far; an important matter considering that both types of Treg are known to be distinct in terms of phenotype and function ( 48 ), and that most clinical trials use either umbilical cord blood- or peripheral blood-derived nTreg ( 49 , 50 ). Furthermore, the in vitro and in vivo function of VitC-treated Treg has not yet been studied, considering that Nikolouli’s report only describes the role of VitC on TGF-β + RA-iTreg differentiated in the presence of allogeneic APCs (without declaring a potential effect of both vitamins on the APCs or the secretion of vitamins from APCs).…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3− T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival

et al. 2018

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Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs). In this study, we measured VitC transporter (SVCT2) expression in different immune cell populations, finding Tregs as one of the cell subset with the highest levels of SVCT2 expression. Unexpectedly, we found that VitC treatment reduces the ability of natural Tregs to suppress effector T cell proliferation in vitro, while having an enhancer effect on TGFβ-induced Foxp3+ Tregs. On the other hand, VitC increases iTregs generation in vitro and in vivo, however, no allograft tolerance was achieved in animals orally treated with VitC. Lastly, Tregs isolated from the draining lymph nodes of VitC-treated and transplanted mice also showed impaired suppression capacity ex vivo. Our results indicate that VitC promotes the generation and expansion of Tregs, without exhibiting CD4+ T cell-mediated allograft tolerance. These observations highlight the relevance of the nutritional status of patients when immune regulation is needed.

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Section: Discussionmentioning

confidence: 99%

Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3− T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival

et al. 2018

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“…[18][19][20] Interestingly, this is being performed despite a limited understanding in regard to how these cells function in vivo. Our work suggests that T regs use multiple mechanisms to prevent T cons activation in vivo, centered on disruption of T con -DC interactions.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] Cotransfer of T regs at the same time as transplantation of donor T cons and TCD BM reduced GVHD in murine models. 13,17 Therefore, we investigated how eT regs impede donor T-cell activation in real time in vivo.…”

Section: Cotransplant Of T Regs Disrupts T Con -Dc Interactionsmentioning

confidence: 99%

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Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD

Lin

Fulton²,

Berginski

et al. 2014

Blood

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“…Low dose IL-2 was chosen to preferentially expand Treg cells without also expanding activated effector T cells. Modulation of IL-2 homeostasis is an important mechanism by which Treg modulates effector differentiation of CD8+ under strongly immunogenic conditions [48,49]. Some authors suggest the use of rapamycin for Treg expansion in vivo with an approximately 75-80% yield of pure cells and total depletion of CD8 and CD19 [50][51][52].…”

Section: Treg-cell Therapymentioning

confidence: 99%

Regulatory T Lymphocytes (Treg): Modulation and Clinical Application

Reichert¹,

Cunha²,

Levy³

et al. 2017

Lymphocyte Updates - Cancer, Autoimmunity and Infection

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Treg cells CD4+CD25+FOXP3+ have a specific function in the tolerance of autoantigens and regulation of the immune response. Modulation of differentiation pathways and the use of Treg cells in cell therapy have been reported in autoimmune diseases, systemic lupus erythromatosis, autoimmune hepatitis, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, bone marrow transplantation and solid organs. The expansion of Treg cells in vivo occurs through low-dose IL-2 treatment. However, because of the heterogeneity and variability of Treg cells, the isolation of peripheral blood cells, through the technique of leucopheresis by GMP (good manuring practice), for in vitro expansion is difficult, necessitating a large combination of specific and reliable cellular markers. Currently, two specific markers, Helios and neuropilin-1, are being studied to facilitate the differentiation of thymus Treg cells and peripheral Treg cells. However, Treg cells induced in vitro are unstable. Modulation of the FOXP3 gene in the CNS1 and CNS2 region is an alternative to maintaining the stability of expanded Treg cells in vitro.

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Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation

Cited by 7 publications

References 109 publications

Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3− T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival

Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3− T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival

Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD

Regulatory T Lymphocytes (Treg): Modulation and Clinical Application

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