Evidence map›Paper›PMID 9603161›Full record

ArticleTransplantation1998

Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control.

J L Contreras, P X Wang, D E Eckhoff, A L Lobashevsky, C Asiedu, L Frenette, M L Robbin, W J Hubbard, S Cartner, S Nadler and 6 more

RetractedAbstract readRetracted Publication
PubMed Publisher
In one paragraph

Article in Transplantation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Induction of transplantation tolerance in non-human primate preclinical models.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2005
    Review
  4. STEALTH in transplantation tolerance.Immunologic research · 2002
    Review
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

J L ContrerasDepartment of Surgery and Transplant Center, University of Alabama at Birmingham, 35294, USA.
P X Wang
D E Eckhoff
A L Lobashevsky
C Asiedu
L Frenette
M L Robbin
W J Hubbard
S Cartner
S Nadler
W J Cook
J Sharff
J Shiloach
F T Thomas
D M Neville
J M Thomas

Funding

PRECLINICAL BRIDGE TO HUMAN TRANSPLANT TOLERANCER01AI039793 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THOMAS, JUDITH M. · 1995 to 2000
$296k
PRECLINICAL MODEL OF ALLOGRAFT TOLERANCER01AI022293 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THOMAS, JUDITH M. · 1985 to 1998
–
NIAID NIH HHS R0I AI39793NIAID NIH HHS R0I AII22293
6 · The paper itself

Abstract

backgroundTolerance is gaining momentum as an approach to reduce lifelong immunosuppressive therapy while improving transplant longevity. Anti-CD3 immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its exceptional ability to deplete sessile lymph node T cells. However, if initiated at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory cytokine response, precluding establishment of tolerance.

methodsFour groups of rhesus monkeys received kidney allografts and immunosuppression. Three groups received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent assay.

resultsSupplementing peritransplant alpha-CD3-IT treatment with a brief course of DSG and MP promoted rejection-free kidney allograft acceptance in 75% of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT, DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody was substituted for IT. Systemic production of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high levels of interleukin (IL)-12 in the first month after transplant, tolerant recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B.

conclusionsIn this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.

Indexed as

Immune ToleranceKidney TransplantationAnimalsAntibodies, MonoclonalCD3 ComplexCytokinesGraft SurvivalGuanidinesImmunosuppressive AgentsImmunotoxinsInflammation MediatorsInterferon-gammaInterleukin-12Macaca mulattaMaleNF-kappa BAntibodies, MonoclonalCD3 ComplexCytokinesGuanidinesgusperimusImmunosuppressive AgentsImmunotoxinsInflammation MediatorsInterferon-gammaInterleukin-12NF-kappa BPhytohemagglutinins

Identifiers

PMID9603161

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.