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Modulation of Phenotype and Function of Human CD4+CD25+ T Regulatory Lymphocytes Mediated by cAMP-Elevating Agents

Overview of attention for article published in Frontiers in immunology, September 2016
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Title
Modulation of Phenotype and Function of Human CD4+CD25+ T Regulatory Lymphocytes Mediated by cAMP-Elevating Agents
Published in
Frontiers in immunology, September 2016
DOI 10.3389/fimmu.2016.00358
Pubmed ID
Authors

Antonella Riccomi, Valentina Gesa, Alessandra Sacchi, Maria Teresa De Magistris, Silvia Vendetti

Abstract

We have shown that cholera toxin (CT) and other cyclic AMP (cAMP)-elevating agents induce upregulation of the inhibitory molecule CTLA-4 in human resting CD4(+) T lymphocytes, which following the treatment acquired suppressive functions. In this study, we evaluated the effect of cAMP-elevating agents on human CD4(+)CD25(+) T cells, which include the T regulatory cells (Tregs) that play a pivotal role in the maintenance of immunological tolerance. We found that cAMP-elevating agents induce upregulation of CTLA-4 in CD4(+)CD25(-) and further enhance its expression in CD4(+)CD25(+) T cells. We observed an increase of two isoforms of mRNA coding for the membrane and the soluble CTLA-4 molecules, suggesting that the regulation of CTLA-4 expression by cAMP is at the transcriptional level. In addition, we found that the increase of cAMP in CD4(+)CD25(+) T cells converts the CD4(+)CD25(+)Foxp3(-) T cells in CD4(+)CD25(+)Foxp3(+) T cells, whereas the increase of cAMP in CD4(+)CD25(-) T cells did not upregulate Foxp3 in the absence of activation stimuli. To investigate the function of these cells, we performed an in vitro suppression assay by culturing CD4(+)CD25(+) T cells untreated or pre-treated with CT with anti-CD3 mAbs-stimulated autologous peripheral blood mononuclear cell. We found that CT enhances the inhibitory function of CD4(+)CD25(+) T cells, CD4(+), and CD8(+) T cell proliferation and IFNγ production are strongly inhibited by CD4(+)CD25(+) T cells pre-treated with cAMP-elevating agents. Furthermore, we found that CD4(+)CD25(+) T lymphocytes pre-treated with cAMP-elevating agents induce the upregulation of CD80 and CD86 co-stimulatory molecules on immature dendritic cells (DCs) in the absence of antigenic stimulation, however without leading to full DC maturation. These data show that the increase of intracellular cAMP modulates the phenotype and function of human CD4(+)CD25(+) T cells.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 1 8%
Unknown 11 92%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 50%
Student > Ph. D. Student 3 25%
Student > Master 2 17%
Other 1 8%
Readers by discipline Count As %
Immunology and Microbiology 8 67%
Biochemistry, Genetics and Molecular Biology 1 8%
Chemical Engineering 1 8%
Agricultural and Biological Sciences 1 8%
Medicine and Dentistry 1 8%
Other 0 0%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 August 2018.
All research outputs
#16,721,208
of 25,373,627 outputs
Outputs from Frontiers in immunology
#18,320
of 31,516 outputs
Outputs of similar age
#203,732
of 327,910 outputs
Outputs of similar age from Frontiers in immunology
#89
of 165 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,516 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,910 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 165 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.