Evaluation of CD4+CD25+/−CD39+ T‐cell populations in peripheral blood of patients following kidney transplantation and during acute allograft rejection

McRae, Jennifer L.; Chia, Joanne S. J.; Pommey, Sandra; Dwyer, Karen M.

doi:10.1111/nep.12894

Cited by 18 publications

(21 citation statements)

References 32 publications

(53 reference statements)

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“…The CD39 is recognized as a marker of cell activation, and its expression in CD4 + CD25‐T cells is linked to higher production of IL‐17a and interferon‐gamma . The accumulation of CD4 + CD25‐CD39 + mTeff cells in the peripheral blood was previously related to lower immune tolerance and poor vaccine responsiveness . In elderly individuals with impaired vaccine response, effector CD4 + CD39 + T cells were characterized by signs of metabolic stress and high susceptibility to apoptosis .…”

Section: Discussionmentioning

confidence: 98%

“…On the other hand, increases in mTreg frequency were related to abrogation of proinflammatory ATP‐dependent effects such as cellular toxicity . In patients following kidney transplantation, the stable frequencies of CD4 + CD25+CD39 + cells were associated with low risk of renal allograft rejection, highlighting its immunosuppression action . In this way, some of the immunoregulatory effects of regular exercise may be attributed to the augment of mTreg CD4 + CD25+CD39 + cells.…”

Section: Discussionmentioning

confidence: 98%

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Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men

Dorneles

Silva

Boeira

et al. 2019

Scandinavian Med Sci Sports

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Funding informationWe are grateful to the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) -Finance Code 001, CAPES (CAPES-PNPD -23038007200/11-08) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) for financial support. PDL, AP, and PRTR also thank CNPq for fellowships.This study investigated the peripheral frequency of monocytes, CD4 + T cell subsets and the systemic levels of cytokines in lean and obese men with different levels of cardiorespiratory fitness (CRF). Mononuclear cells were obtained from 45 lean and 45 obese men who were assigned into six groups according to their body mass index and CRF (low, moderate, or high VO 2Peak ) to analyze the frequency of monocyte subsets and subpopulations of CD4 + T cells (Treg cells, CD4 + CD25 high CD127 low ; mTeff, CD4 + CD25-CD39+; mTreg, CD4 + CD25+CD39+). The systemic levels of interleukin (IL)-6, IL-10, IL-17a, IL-33, leptin, and tumor necrosis factor-alpha (TNF-α) were also evaluated. Seven sedentary obese men performed one week of high-intensity interval training (HIIT, 3 sessions/week), and blood samples were collected before and 24 hours after the last session for phenotypic analysis of T cells and monocytes. Obese individuals presented an inflammatory profile characterized by lower frequencies of Treg and mTreg cells and higher proportions of proinflammatory monocytes. However, higher CRF status increased the frequencies of Treg cells and mTreg cells and decreased the percentage of CD4 + mTeff cells and intermediate and non-classical monocytes in the peripheral blood from lean and obese men. Systemic lower levels of proinflammatory (IL-6 and TNF-) cytokines and higher concentrations of IL-10 and IL-33 were observed in moderate and higher CRF in all subjects. HIIT increased the proportions of circulating mTreg and Treg cells in sedentary obese individuals. The immunoregulatory role of CRF contributes to the maintenance of low levels of inflammatory mediators. K E Y W O R D S CD39, CD73, exercise, inflammation, monocyte subsets, obesity, T cells, Treg cells, VO 2 peak 1756 | DORNELES Et aL. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Dorneles GP, da Silva I, Boeira MC, et al. Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men. Scand J Med Sci Sports.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men

Dorneles

Silva

Boeira

et al. 2019

Scandinavian Med Sci Sports

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“…The CD4 + CD25-CD39 + T cell phenotype presents signs of metabolic stress (i.e. alterations in redox state) and high susceptibility to apoptosis 58 , and these cells were previously related to lower immune tolerance 59 . It was previously reported that exhaustive exercise leads to higher CD4 + Th17 phenotype and lowered Treg counts in the peripheral blood of highly trained men 60 .…”

Section: Discussionmentioning

confidence: 99%

Immunoregulation induced by autologous serum collected after acute exercise in obese men: a randomized cross-over trial

Dorneles

Silva

Santos

et al. 2020

Sci Rep

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In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts—high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue—in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

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“…This lack of degradation capacity was not due to immunosuppressive treatments. Finally, a reduced mTreg and mTeff cells expressing CD39 was observed in patients with acute cellular rejection, and mTreg cells in transplant patients with stable graft function displayed more potent suppressive capacity than those of non-immunosuppressed controls ( 106 ). Thus, the authors of those findings propose that determining changes within these T cell subsets could help identify patients at risk of renal allograft rejection and, furthermore, that they could be considered for clinical purposes due to their suppressive properties.…”

Section: Manipulating the Metabolic Pathway In Transplantationmentioning

confidence: 99%

Regulation of the Immune Response by the Inflammatory Metabolic Microenvironment in the Context of Allotransplantation

2018

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Antigen challenge induced by allotransplantation results in the activation of T and B cells, followed by their differentiation and proliferation to mount an effective immune response. Metabolic fitness has been shown to be crucial for supporting the major shift from quiescent to active immune cells and for tuning the immune response. Metabolic reprogramming includes regulation of the balance between glycolysis and mitochondrial respiration processes. Recent research has shed new light on the functions served by the end products of metabolism such as lactate, acetate, and ATP. At enhanced local concentrations, these metabolites have complex effects in which they not only induce T and B cell responses, cell mobility, and cytokine secretion but also favor the resolution of inflammation by promoting regulatory functions. Such mechanisms are instrumental in the context of the immune response in transplantation, not only to protect the graft and/or eliminate cells targeting it but also to maintain cell homeostasis per se. Metabolic adaptation thus plays an instrumental role on the outcome of the cellular and humoral responses. This, of course, raises the possibility of drugs that would interfere in these metabolic pathways to control the immune response but also highlights the risk that some drugs may perturb this metabolism and cell homeostasis and be deleterious for graft outcome. This review focuses on how metabolic alterations of the local immune microenvironment regulate the immune response and the impact of metabolic manipulation in allotransplantation.

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Evaluation of CD4⁺CD25^+/−CD39⁺ T‐cell populations in peripheral blood of patients following kidney transplantation and during acute allograft rejection

Cited by 18 publications

References 32 publications

Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men

Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men

Immunoregulation induced by autologous serum collected after acute exercise in obese men: a randomized cross-over trial

Regulation of the Immune Response by the Inflammatory Metabolic Microenvironment in the Context of Allotransplantation

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