OBJECTIVE—NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade–based tolerance protocols have failed in prolonging islet allograft survival in NOD mice

A. A. Rossini

Bottini

D'Cruz

D. L. Greiner

D. V. Serreze

del Rio

Fontenot

Hill

Hunter

Iwakoshi

J. Mangada

Kishimoto

Kissler

Koulmanda

Kr  mer

L. B. Peterson

L. D. Shultz

L. S. Wicker

Lyons

M. A. Brehm

Markees

Molano

Pearson

Penha-Goncalves

Podolin

Prinz

Rabinovitch

Refaeli

Robles

ROSSINI

Seung

Shrikant

Shultz

T. Pearson

Thornton

Todd

Ueda

Vang

Wicker

Yamanouchi

English

PubMed

Crossref

Idd Loci Synergize to Prolong Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice

OBJECTIVE: NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade-based tolerance protocols have failed    in prolonging islet allograft survival in NOD mice. RESEARCH DESIGN AND METHODS: To investigate the underlying mechanisms, we studied the ability of costimulation blockade to prolong islet allograft survival in congenic NOD mice bearing    insulin-dependent diabetes (Idd) loci that reduce the frequency of diabetes. RESULTS: The frequency of diabetes is reduced in NOD.B6 Idd3 mice and is virtually absent in NOD.B6/B10 Idd3 Idd5 mice. Islet allograft survival in NOD.B6 Idd3 mice    treated with costimulation blockade is prolonged compared with NOD mice, and in NOD.B6/B10 Idd3 Idd5, mice islet allograft survival is similar to that achieved in C57BL/6 mice. Conversely, some Idd loci were not beneficial for the induction of    transplantation tolerance. Alloreactive CD8 T-cell depletion in (NOD x CBA)F1 mice treated with costimulation blockade was impaired compared with similarly treated (C57BL/6.H2(g7) x CBA)F1 mice. Injection of exogenous interleukin (IL)-2 into NOD    mice treated with costimulation prolonged islet allograft survival. NOD.B6 Idd3 mice treated with costimulation blockade deleted alloreactive CD8 T-cells and exhibited prolonged islet allograft survival.  CONCLUSIONS: Il2 is the Idd3 diabetes    susceptibility gene and can influence the outcome of T-cell deletion and islet allograft survival in mice treated with costimulation blockade. These data suggest that Idd loci can facilitate induction of transplantation tolerance by costimulation    blockade and that IL-2/Idd3 is a critical component in this process

Mangada, J

Pearson, T

Brehm, M A

Wicker, L S

Peterson, L B

Shultz, L D

Serreze, D V

Rossini, A A

Greiner, D L

The Jackson Laboratory: The Mouseion at the JAXlibrary

Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice.

OBJECTIVE: NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade-based tolerance protocols have failed in prolonging islet allograft survival in NOD mice. RESEARCH DESIGN AND METHODS: To investigate the underlying mechanisms, we studied the ability of costimulation blockade to prolong islet allograft survival in congenic NOD mice bearing insulin-dependent diabetes (Idd) loci that reduce the frequency of diabetes. RESULTS: The frequency of diabetes is reduced in NOD.B6 Idd3 mice and is virtually absent in NOD.B6/B10 Idd3 Idd5 mice. Islet allograft survival in NOD.B6 Idd3 mice treated with costimulation blockade is prolonged compared with NOD mice, and in NOD.B6/B10 Idd3 Idd5, mice islet allograft survival is similar to that achieved in C57BL/6 mice. Conversely, some Idd loci were not beneficial for the induction of transplantation tolerance. Alloreactive CD8 T-cell depletion in (NOD x CBA)F1 mice treated with costimulation blockade was impaired compared with similarly treated (C57BL/6.H2(g7) x CBA)F1 mice. Injection of exogenous interleukin (IL)-2 into NOD mice treated with costimulation prolonged islet allograft survival. NOD.B6 Idd3 mice treated with costimulation blockade deleted alloreactive CD8 T-cells and exhibited prolonged islet allograft survival. CONCLUSIONS: Il2 is the Idd3 diabetes susceptibility gene and can influence the outcome of T-cell deletion and islet allograft survival in mice treated with costimulation blockade. These data suggest that Idd loci can facilitate induction of transplantation tolerance by costimulation blockade and that IL-2/Idd3 is a critical component in this process

Mangada, Julie A.

Pearson, Todd

Brehm, Michael A.

Wicker, Linda S.

Peterson, Laurence B.

Shultz, Leonard D.

Serreze, David V.

Rossini, Aldo A.

Greiner, Dale L.

eScholarship@UMassChan

Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice

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Idd Loci Synergize to Prolong Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice

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