Evidence map›Paper›PMID 22390202›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2012

Ex vivo expansion of human Tregs by rabbit ATG is dependent on intact STAT3-signaling in CD4⁺ T cells and requires the presence of monocytes.

O Boenisch, M Lopez, W Elyaman, C N Magee, U Ahmad, N Najafian

Open access · greenAbstract read
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Induction of Clinical Operational Tolerance Through Immunosuppression Minimization: Less Is More?Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells.Journal of the American Society of Nephrology : JASN · 2017
    Review
  13. Article
  14. Regulatory T Cell Infusion Can Enhance Memory T Cell and Alloantibody Responses in Lymphodepleted Nonhuman Primate Heart Allograft Recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  15. Sequential monitoring and stability of ex vivo-expanded autologous and nonautologous regulatory T cells following infusion in nonhuman primates.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2015
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Regulatory T cell induction, migration, and function in transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2012
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

O BoenischTransplantation Research Center, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
M Lopez
W Elyaman
C N Magee
U Ahmad
N Najafian
Brigham and Women's Hospital · USHarvard University · US

Funding

Novel Therapies to Improve Renal and Cardiac Allograft OutcomesU01AI063623 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI CHANDRAKER, ANIL · 2004 to 2013
$30.9M
NIAID NIH HHS U01 AI 063623NIAID NIH HHS U01 AI063623
6 · The paper itself

Abstract

The addition of low, nondepleting doses of rabbit antithymocyte globulin (ATG) to human peripheral blood mononuclear cells has been shown to expand functional CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) in vitro. This report is the first to elucidate the exact cellular mechanisms of ATG-mediated Treg expansion. CD4(+) T cells require monocytes, but not other antigen presenting cell subsets, to be present in coculture to expand Tregs. However, T cells do not require direct cell-cell contact with monocytes, suggesting the importance of soluble factors. Moreover, ATG initially "reprograms" CD4(+) T cells, but not monocytes, and induces STAT3 and STAT5 signaling in CD4(+) cells. These reprogrammed CD4(+) T cells subsequently secrete GM-CSF and IL-10 only in case of intact STAT3 signaling, which in turn promote the generation of tolerogenic CD14(+) CD11c(+) dendritic cells characterized by enhanced IL-10 and decreased IL-12 production. Treg expansion following ATG treatment is accompanied by enhanced gene expression of both GM-CSF and Bcl-2, but not TGF-β, in peripheral blood mononuclear cells. These results demonstrate that ex vivo expansion of human Tregs by ATG is due to its ability to reprogram CD4(+) T cells in a STAT3-dependent but TGF-β-independent manner, leading to the generation of monocyte-derived dendritic cells with a tolerogenic cytokine profile.

Indexed as

AnimalsAntilymphocyte SerumCD4-Positive T-LymphocytesCell ProliferationCells, CulturedCytokinesDendritic CellsFlow CytometryGranulocyte-Macrophage Colony-Stimulating FactorHumansImmunosuppressive AgentsLeukocytes, MononuclearMonocytesRabbitsReal-Time Polymerase Chain ReactionRNA, MessengerAntilymphocyte SerumCytokinesGranulocyte-Macrophage Colony-Stimulating FactorImmunosuppressive AgentsRNA, MessengerSTAT3 Transcription FactorTransforming Growth Factor beta

Identifiers

PMID22390202
PMCPMC3777828
OpenAlexW1832208952

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.