Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody

Ruth Molano, Antonello Pileggi, Thierry Berney, Raffaella Poggioli, Elsie Zahr, Robert Oliver, Thomas Malek, Camillo Ricordi, Luca A Inverardi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background. Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice. Methods. C57BL/6 islets were transplanted under the kidney capsule of spontaneously diabetic NOD mice. Treatment consisted of a combination of rapamycin, tacrolimus, and anti-interleukin (IL)-2 monoclonal antibody. Control groups received each treatment alone, a combination of two agents, or no treatment. Results. Untreated animals invariably lost their graft within 13 days. Administration of rapamycin and tacrolimus significantly prolonged graft survival, with two of seven animals bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody therapy further improved graft survival, with six of eight grafts functioning longer than 100 days and two of eight grafts functioning longer than 200 days. Conclusions. In view of the limited success obtained with other treatments in this model, the dramatic prolongation of graft survival observed in the authors' study, by using a therapy that mimics one successfully used in clinical trials, seems to validate the NOD mouse as a meaningful model for the study of therapeutic interventions for the prevention of islet graft loss.

Original languageEnglish
Pages (from-to)1812-1819
Number of pages8
JournalTransplantation
Volume75
Issue number11
DOIs
StatePublished - Jun 15 2003

Fingerprint

Inbred NOD Mouse
Tacrolimus
Sirolimus
Interleukin-2
Allografts
Antibodies
Transplants
Graft Survival
Therapeutics
Clinical Trials
Islets of Langerhans Transplantation
Autoimmunity
Type 1 Diabetes Mellitus
Capsules
Monoclonal Antibodies
Kidney
Recurrence
Control Groups
Survival

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody. / Molano, Ruth; Pileggi, Antonello; Berney, Thierry; Poggioli, Raffaella; Zahr, Elsie; Oliver, Robert; Malek, Thomas; Ricordi, Camillo; Inverardi, Luca A.

In: Transplantation, Vol. 75, No. 11, 15.06.2003, p. 1812-1819.

Research output: Contribution to journalArticle

Molano, Ruth ; Pileggi, Antonello ; Berney, Thierry ; Poggioli, Raffaella ; Zahr, Elsie ; Oliver, Robert ; Malek, Thomas ; Ricordi, Camillo ; Inverardi, Luca A. / Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody. In: Transplantation. 2003 ; Vol. 75, No. 11. pp. 1812-1819.
@article{6bd53234879b4d3f8160bec328d2add7,
title = "Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody",
abstract = "Background. Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice. Methods. C57BL/6 islets were transplanted under the kidney capsule of spontaneously diabetic NOD mice. Treatment consisted of a combination of rapamycin, tacrolimus, and anti-interleukin (IL)-2 monoclonal antibody. Control groups received each treatment alone, a combination of two agents, or no treatment. Results. Untreated animals invariably lost their graft within 13 days. Administration of rapamycin and tacrolimus significantly prolonged graft survival, with two of seven animals bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody therapy further improved graft survival, with six of eight grafts functioning longer than 100 days and two of eight grafts functioning longer than 200 days. Conclusions. In view of the limited success obtained with other treatments in this model, the dramatic prolongation of graft survival observed in the authors' study, by using a therapy that mimics one successfully used in clinical trials, seems to validate the NOD mouse as a meaningful model for the study of therapeutic interventions for the prevention of islet graft loss.",
author = "Ruth Molano and Antonello Pileggi and Thierry Berney and Raffaella Poggioli and Elsie Zahr and Robert Oliver and Thomas Malek and Camillo Ricordi and Inverardi, {Luca A}",
year = "2003",
month = "6",
day = "15",
doi = "10.1097/01.TP.0000064622.54799.0E",
language = "English",
volume = "75",
pages = "1812--1819",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody

AU - Molano, Ruth

AU - Pileggi, Antonello

AU - Berney, Thierry

AU - Poggioli, Raffaella

AU - Zahr, Elsie

AU - Oliver, Robert

AU - Malek, Thomas

AU - Ricordi, Camillo

AU - Inverardi, Luca A

PY - 2003/6/15

Y1 - 2003/6/15

N2 - Background. Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice. Methods. C57BL/6 islets were transplanted under the kidney capsule of spontaneously diabetic NOD mice. Treatment consisted of a combination of rapamycin, tacrolimus, and anti-interleukin (IL)-2 monoclonal antibody. Control groups received each treatment alone, a combination of two agents, or no treatment. Results. Untreated animals invariably lost their graft within 13 days. Administration of rapamycin and tacrolimus significantly prolonged graft survival, with two of seven animals bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody therapy further improved graft survival, with six of eight grafts functioning longer than 100 days and two of eight grafts functioning longer than 200 days. Conclusions. In view of the limited success obtained with other treatments in this model, the dramatic prolongation of graft survival observed in the authors' study, by using a therapy that mimics one successfully used in clinical trials, seems to validate the NOD mouse as a meaningful model for the study of therapeutic interventions for the prevention of islet graft loss.

AB - Background. Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice. Methods. C57BL/6 islets were transplanted under the kidney capsule of spontaneously diabetic NOD mice. Treatment consisted of a combination of rapamycin, tacrolimus, and anti-interleukin (IL)-2 monoclonal antibody. Control groups received each treatment alone, a combination of two agents, or no treatment. Results. Untreated animals invariably lost their graft within 13 days. Administration of rapamycin and tacrolimus significantly prolonged graft survival, with two of seven animals bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody therapy further improved graft survival, with six of eight grafts functioning longer than 100 days and two of eight grafts functioning longer than 200 days. Conclusions. In view of the limited success obtained with other treatments in this model, the dramatic prolongation of graft survival observed in the authors' study, by using a therapy that mimics one successfully used in clinical trials, seems to validate the NOD mouse as a meaningful model for the study of therapeutic interventions for the prevention of islet graft loss.

UR - http://www.scopus.com/inward/record.url?scp=0037708577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037708577&partnerID=8YFLogxK

U2 - 10.1097/01.TP.0000064622.54799.0E

DO - 10.1097/01.TP.0000064622.54799.0E

M3 - Article

C2 - 12811239

AN - SCOPUS:0037708577

VL - 75

SP - 1812

EP - 1819

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 11

ER -