Evidence map›Paper›PMID 29319621›Full record

ArticleTransplantation2018

Selective CD28 Inhibition Modulates Alloimmunity and Cardiac Allograft Vasculopathy in Anti-CD154-Treated Monkeys.

Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Leukocyte dynamics inFrontiers in immunology · 2025
    Article
  2. Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  3. Article
  4. Article
  5. Review
  6. 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

17 authors at 1 institution in 1 country.

Tianshu ZhangDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Agnes M AzimzadehDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Wenji SunDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Natalie A O'NeillDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Evelyn SievertDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Emily BergbowerDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Gheorghe BraileanuDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Lars BurdorfDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Xiangfei ChengDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Thomas MonahanDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Siamak DahiDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Donald G HarrisDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Elana RybakDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Emily WeltyDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Anthony KronfliDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Chris AvonDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
Richard N PiersonDivision of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.
University of Maryland, Baltimore · US

Funding

Nonhuman Primate Reagent ResourceU24AI126683 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Diogo Magnani · 2016 to 2026
$20.1M
Immunomodulation for Heart Allograft ToleranceU01AI066719 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PIERSON, RICHARD N · 2005 to 2016
$8.5M
Resource for Nonhuman Primate Cell Depleting AntibodiesR24OD010976 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ENGELMAN, KATHLEEN, MAGNANI, DIOGO · 2012 to 2019
$4.7M
NIAID NIH HHS U01 AI066719NIAID NIH HHS U24 AI126683NIH HHS R24 OD010976
6 · The paper itself

Abstract

backgroundSelective CD28 inhibition is actively pursued as an alternative to B7 blockade using cytotoxic T lymphocyte antigen 4 Ig based on the hypothesis that the checkpoint immune regulators cytotoxic T lymphocyte antigen 4 and programmed death ligand 1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single-chain anti-CD28 Fv fragment linked to alpha-1 antitrypsin [sc28AT]) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week "induction" sc28AT treatment with prolonged CD154 blockade.

methodsCynomolgus monkey heterotopic cardiac allograft recipients received sc28AT (10 mg/kg, d0-20, n = 3), hu5C8 (10-30 mg/kg, d0-84, n = 4), or combination (n = 6). Graft survival was monitored by telemetry. Protocol biopsies and graft explants were analyzed for International Society of Heart and Lung Transplantation acute rejection grade and cardiac allograft vasculopathy score. Alloantibody, T-cell phenotype and regulatory T cells were analyzed by flow cytometry. Immunochemistry and gene expression (NanoString) characterized intra-graft cellular infiltration.

resultsRelative to modest prolongation of median graft survival time with sc28AT alone (34 days), hu5C8 (133 days), and sc28AT + hu5C8 (141 days) prolonged survival to a similar extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the severity of acute rejection and cardiac allograft vasculopathy during the first 3 months after transplantation relative to hu5C8 alone. These findings were associated with decreased proportions of circulating CD8 and CD3CD28 T cells, and modulation of inflammatory gene expression within allografts.

conclusionsInduction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants.

Indexed as

AnimalsCD28 AntigensCD40 LigandGraft SurvivalHeart TransplantationImmunophenotypingMacaca fascicularisTissue DonorsTransplantation, HomologousVascular DiseasesCD28 AntigensCD40 Ligand

Identifiers

PMID29319621
PMCPMC5820224
OpenAlexW2783703577

What OpenQuestion holds

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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.