Evidence map›Paper›PMID 22300641›Full record

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

Regulatory T cells exhibit decreased proliferation but enhanced suppression after pulsing with sirolimus.

K Singh, N Kozyr, L Stempora, A D Kirk, C P Larsen, B R Blazar, L S Kean

Abstract 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 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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

29 citing papers in PubMed.

  1. Review
  2. Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Induction of Immunosuppressive CD8Journal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  9. Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells.Journal of the American Society of Nephrology : JASN · 2017
    Review
  10. Article
  11. Article
  12. Review
  13. 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
  14. Review
  15. Article
  16. Article
  17. 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
  18. Article
  19. Article
  20. Superiority of rapamycin over tacrolimus in preserving nonhuman primate Treg half-life and phenotype after adoptive transfer.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014
    Article
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

7 authors.

K SinghThe Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
N Kozyr
L Stempora
A D Kirk
C P Larsen
B R Blazar
L S Kean

Funding

YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI ALTMAN, JOHN DAVID · 1985 to 2011
$114.0M
Transplant Tolerance in Non-Human PrimatesU19AI051731 · NIAID · UNIVERSITY OF WESTERN ONTARIO · PI LARSEN, CHRISTIAN P. · 2002 to 2022
$54.1M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025008 · NCRR · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2007 to 2011
$29.0M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI CUTLER, COREY S · 2009 to 2019
$17.5M
SPF BREEDING COLONIES AT THE YERKES NPRC: AIDS, THERAPEUTIC AGENT DVMTU24RR018109 · NCRR · EMORY UNIVERSITY · PI ELSE, JAMES GIBSON · 2002 to 2011
$13.8M
Novel Biologic Therapies for GVHDR01HL095791 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI KEAN, LESLIE S · 2010 to 2025
$13.3M
TRANSPLANT TOLERANCE--COSTIMULATION, CYTOKINES &CHIMERISMP01AI044644 · NIAID · EMORY UNIVERSITY · PI LARSEN, CHRISTIAN P. · 1998 to 2010
$9.7M
IN VIVO PREVENTION OF MURINE GVHDR01AI034495 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1993 to 2016
$6.2M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
NCATS NIH HHS UL1 TR000454NCI NIH HHS F32 CA067493NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA 067493NCI NIH HHS P01 CA142106NCRR NIH HHS 2U24 RR018109NCRR NIH HHS P51 RR000165NCRR NIH HHS U24 RR018109NCRR NIH HHS UL1 RR025008NHLBI NIH HHS 1R01 HL095791NHLBI NIH HHS HL 56067NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL095791NHLBI NIH HHS R37 HL056067NIAID NIH HHS 2P01 AI044644NIAID NIH HHS 2U19 AI051731NIAID NIH HHS 5K08 AI065822NIAID NIH HHS K08 AI065822NIAID NIH HHS P01 AI044644NIAID NIH HHS P01 AI056299NIAID NIH HHS R01 AI034495NIAID NIH HHS R01 AI34495NIAID NIH HHS U01 AI079223NIAID NIH HHS U19 AI051731
6 · The paper itself

Abstract

Although regulatory T cells (Tregs) suppress allo-immunity, difficulties in their large-scale production and in maintaining their suppressive function after expansion have thus far limited their clinical applicability. Here we have used our nonhuman primate model to demonstrate that significant ex vivo Treg expansion with potent suppressive capacity can be achieved and that Treg suppressive capacity can be further enhanced by their exposure to a short pulse of sirolimus. Both unpulsed and sirolimus-pulsed Tregs (SPTs) are capable of inhibiting proliferation of multiple T cell subpopulations, including CD4(+) and CD8(+) T cells, as well as antigen-experienced CD28(+) CD95(+) memory and CD28(-) CD95(+) effector subpopulations. We further show that Tregs can be combined in vitro with CTLA4-Ig (belatacept) to lead to enhanced inhibition of allo-proliferation. SPTs undergo less proliferation in a mixed lymphocyte reaction (MLR) when compared with unpulsed Tregs, suggesting that Treg-mediated suppression may be inversely related to their proliferative capacity. SPTs also display increased expression of CD25 and CTLA4, implicating signaling through these molecules in their enhanced function. Our results suggest that the creation of SPTs may provide a novel avenue to enhance Treg-based suppression of allo-immunity, in a manner amenable to large-scale ex vivo expansion and combinatorial therapy with novel, costimulation blockade-based immunosuppression strategies.

Indexed as

AnimalsAntigens, CDCell ProliferationFlow CytometryImmunosuppressive AgentsMacaca mulattaSirolimusT-Lymphocytes, RegulatoryAntigens, CDImmunosuppressive AgentsSirolimus

Identifiers

PMID22300641
PMCPMC3471086

What OpenQuestion holds

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Registered trials

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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.