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- Mougiakakos, D, et al.
(author)
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Increased thioredoxin-1 production in human naturally occurring regulatory T cells confers enhanced tolerance to oxidative stress
- 2011
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:3, s. 857-861
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Journal article (peer-reviewed)abstract
- Levels of regulatory T cells (Tregs) are increased in different cancer types as well as in inflammatory diseases, such as rheumatoid arthritis. Treg accumulation may result from aberrant proliferation and trafficking as well as greater resilience to oxidative stress compared with conventional T cells. This enhanced antioxidative capacity of Tregs possibly serves as feedback inhibition during inflammation and prevents uncontrolled immune reactions by favoring survival of suppressor rather than effector cells. In this study, we demonstrate that human Tregs express and secrete higher levels of thioredoxin-1, a major antioxidative molecule. Thioredoxin-1 has an essential role in maintaining their surface thiol density as the first line of antioxidative defense mechanisms and is sensitive to proinflammatory stimuli, mainly tumor necrosis factor-α, in a nuclear factor-κB-dependent fashion. The antiapoptotic and oncogenic potential of (secreted) Trx-1 suggests that it may exert effects in Tregs beyond redox regulation.
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- Jitschin, R, et al.
(author)
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Alterations in the cellular immune compartment of patients treated with third-party mesenchymal stromal cells following allogeneic hematopoietic stem cell transplantation
- 2013
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In: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 31:8, s. 1715-1725
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Journal article (peer-reviewed)abstract
- Adoptive transfer of third-party mesenchymal stromal cells (MSCs) has emerged as a promising tool for the treatment of steroid-refractory graft-versus-host disease (GVHD). Despite numerous in vitro studies and preclinical models, little is known about their effects on the patients' immune system. We assessed immune alterations in the T-cell, B-cell, natural killer cell, dendritic cell, and monocytic compartments of steroid-refractory GVHD patients 30, 90, and 180 days after MSC (n = 6) or placebo (n = 5) infusion, respectively. Infused MSCs were bioactive as suggested by the significant reduction in epithelial cell death, which represents a biomarker for acute GVHD. There were several indications that MSCs shift the patients' immune system toward a more tolerogenic profile. Most importantly, infusion of MSCs was associated with increased levels of regulatory (forkhead box P3 (FOXP3)+ and interleukin (IL)-10+) T-cells, reduced pro-inflammatory IL-17+ T(Th17)-cells, and skewing toward type-2 T-helper cell responses. Furthermore, IL-2, which has been recently shown to exert a positive immune modulating effect in GVHD patients, was higher in the MSC patients at all evaluated time points during 6 months after MSC-infusion. Overall, our findings will contribute to the refinement of monitoring tools, for assessing MSC treatment-efficacy and increase our understanding regarding the MSCs' in vivo effects.
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