Evidence map›Paper›PMID 12409674›Full record

ArticleAnnals of surgery2002

New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs.

Masayuki Sho, Sigrid E Sandner, Nader Najafian, Alan D Salama, Victor Dong, Akira Yamada, Koji Kishimoto, Hiroshi Harada, Isabela Schmitt, Mohamed H Sayegh

Open access · greenAbstract read
In one paragraph

Article in Annals of surgery, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. The role of costimulatory molecules in directing the functional differentiation of alloreactive T helper cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012
    Review
  6. Implication for transglutaminase 2-mediated activation of β-catenin signaling in neointimal vascular smooth muscle cells in chronic cardiac allograft rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2012
    Article
  7. Article
  8. Selective CD28 blockade attenuates acute and chronic rejection of murine cardiac allografts in a CTLA-4-dependent manner.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011
    Article
  9. Article
  10. Article
  11. Article
  12. Divergent role of donor dendritic cells in rejection versus tolerance of allografts.Journal of the American Society of Nephrology : JASN · 2009
    Article
  13. Article
  14. Transplantation tolerance: lessons from experimental rodent models.Transplant international : official journal of the European Society for Organ Transplantation · 2007
    Review
  15. Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2007
    Article
  16. Article
  17. Article
  18. Review
  19. Targeting CD40L: a promising therapeutic approach.Clinical and diagnostic laboratory immunology · 2004
    Review
  20. 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

10 authors at 1 institution in 1 country.

Masayuki ShoLaboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sigrid E Sandner
Nader Najafian
Alan D Salama
Victor Dong
Akira Yamada
Koji Kishimoto
Hiroshi Harada
Isabela Schmitt
Mohamed H Sayegh
Brigham and Women's Hospital · US

Funding

T Cell Fate as a Determinant of Alloimmune ResponsesP01AI041521 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI TURKA, LAURENCE A · 1997 to 2011
$15.9M
INTRATHYMIC TRANSPLANTATION TOLERANCE BY MHC PEPTIDESR01AI034965 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI SAYEGH, MOHAMED H · 1999 to 2003
$1.3M
NIAID NIH HHS P01 AI041521NIAID NIH HHS R01 AI034965
6 · The paper itself

Abstract

objectiveTo determine the precise in vivo interaction between T-cell costimulatory blockade and conventional immunosuppression in transplantation. SUMMARY BACKGROUND DATA: Blocking B7 or CD154 T-cell costimulatory activation pathways prevents allograft rejection in small and large animal transplant models and is considered a promising strategy for clinical organ transplantation.

methodsA fully MHC-mismatched vascularized mouse cardiac allograft model was used to test the interactions between anti-CD154 or CTLA4Ig monotherapy and conventional immunosuppressive drugs in promoting long-term graft acceptance. The frequency of alloreactive T cell was measured by ELISPOT. Chronic rejection was examined by histology.

resultsCyclosporine, tacrolimus, and anti-IL-2R monoclonal antibody therapy abrogated the effect of a single-dose protocol of anti-CD154 therapy. In contrast, rapamycin acted synergistically with anti-CD154 therapy in promoting long-term allograft survival. The addition of calcineurin inhibitors did not abolish this synergistic effect. Intense CD154-CD40 blockade by a multiple-dose schedule of anti-CD154 resulted in long-term graft survival and profound alloreactive T-cell unresponsiveness and overcame the opposite effects of calcineurin inhibitors. CTLA4Ig induced long-term graft survival, and the effect was not affected by the concomitant use of any immunosuppressive drugs.

conclusionsThe widespread view that calcineurin inhibitors abrogate the effects of T-cell costimulatory blockade should be revisited. Sufficient costimulatory blockade and synergy induced by CD154 blockade and rapamycin promote allograft tolerance and prevent chronic rejection.

Indexed as

Heart TransplantationImmunoconjugatesAbataceptAnimalsAntibodies, MonoclonalAntigens, CDAntigens, DifferentiationCalcineurin InhibitorsCD40 LigandCTLA-4 AntigenCyclosporineGraft RejectionImmunoglobulin Fc FragmentsImmunosuppressive AgentsMethylprednisoloneMiceAbataceptAntibodies, MonoclonalAntigens, CDAntigens, DifferentiationCalcineurin InhibitorsCD40 LigandCTLA-4 AntigenCtla4 protein, mouseCyclosporineImmunoconjugatesImmunoglobulin Fc FragmentsImmunosuppressive AgentsMethylprednisoloneSirolimusTacrolimus

Identifiers

PMID12409674
PMCPMC1422626
OpenAlexW2127882613

What Socratic 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 Socratic graph.