Evidence map›Paper›PMID 22878670›Full record

ArticleIslets

Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet allograft survival.

Xiaojie Wang, Jianqiang Hao, Daniel L Metzger, Alice Mui, I-Fang Lee, Noushin Akhoundsadegh, C Lieping Chen, Dawei Ou, Ziliang Ao, C Bruce Verchere and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Islets. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 36% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. 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

11 authors at 2 institutions in 2 countries.

Xiaojie WangDepartment of Surgery, University of British Columbia, Vancouver, BC, Canada.
Jianqiang Hao
Daniel L Metzger
Alice Mui
I-Fang Lee
Noushin Akhoundsadegh
C Lieping Chen
Dawei Ou
Ziliang Ao
C Bruce Verchere
Garth L Warnock
University of British Columbia · CAYale University · US

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Costimulation blockade is an effective way to prevent allograft rejection. In this study, we tested the efficacy of two negative co-signaling molecules in protecting islet allograft function. We used local expression of B7-H4 by adenoviral transduction of islets (Ad-B7-H4) and systemic administration of CTLA-4.Ig to investigate the outcomes of allograft survival. Five groups of streptozotocin-induced diabetic C57BL/6 mice received 400 islets each from BALB/c donors. The groups consisted of control (G1); CTLA-4.Ig (G2); Ad-LacZ (G3); Ad-B7-H4 (G4); and Ad-B7-H4 and CTLA-4.Ig combined (G5). G1 and G3 developed graft failure on average of two weeks. G2, G4 and G5 survived for 43.8 ± 34.8, 54.7 ± 31.2 and 77.8 ± 21.5 d, respectively. Activated T and B cells in the lymph nodes were significantly controlled by CTLA-4.Ig treatment. Significantly reduced infiltrates were also detected in the allografts of G2 compared with G1. By contrast, B7-H4 significantly inhibited Th1-associated IFN-gamma secretion in the early stage and increased Foxp3 (+) T cells in the long-term surviving allografts. Our study suggests that CTLA-4 and B7-H4 inhibit alloimmune responses through distinct mechanisms, and that combination therapy which activates two negative co-signaling pathways can further enhance islet allograft survival.

Indexed as

Islets of Langerhans TransplantationSignal TransductionAnalysis of VarianceAnimalsB-LymphocytesCD28 AntigensCTLA-4 AntigenDiabetes Mellitus, ExperimentalFemaleForkhead Transcription FactorsGraft SurvivalImmunoglobulinsInsulinInsulin SecretionInterferon-gammaKaplan-Meier EstimateCD28 AntigensCTLA-4 AntigenForkhead Transcription FactorsFoxp3 protein, mouseImmunoglobulinsInsulinInterferon-gammaV-Set Domain-Containing T-Cell Activation Inhibitor 1Vtcn1 protein, mouse

Identifiers

PMID22878670
PMCPMC3496653
OpenAlexW2037804128

What OpenQuestion holds

Textmetadata
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.