Melatonin prolongs islet graft survival in diabetic NOD mice

2009 ◽  
Vol 47 (3) ◽  
pp. 284-292 ◽  
Author(s):  
Gu-Jiun Lin ◽  
Shing-Hwa Huang ◽  
Yuan-Wu Chen ◽  
Dueng-Yuan Hueng ◽  
Ming-Wei Chien ◽  
...  
Keyword(s):  
Graft Survival ◽  
Nod Mice ◽  
Islet Graft

Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Survival ◽  
Tolerance Induction ◽  
Nod Mice ◽  
Disease Recurrence ◽  
Nod Mouse ◽  
Islet Graft ◽  
Specific Effector ◽  
Syngeneic Islet Transplantation ◽  
Specific Tolerance

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4<sup>+</sup> T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

scholarly journals Long-Term Islet Graft Survival in NOD Mice by Abrogation of Recurrent Autoimmunity

Diabetes ◽  
2004 ◽  
Vol 53 (9) ◽  
pp. 2338-2345 ◽  
Author(s):  
Q. Shi ◽  
D. Wang ◽  
G. A. Hadley ◽  
A. W. Bingaman ◽  
S. T. Bartlett ◽  
...  
Keyword(s):  
Graft Survival ◽  
Nod Mice ◽  
Islet Graft

EFFECT OF THERAPY WITH NON-DEPLETING ANTI-CD4 MONOCLONAL ANTIBODY AND CTLA4IG ON ALLOGENEIC ISLET GRAFT SURVIVAL IN AUTOIMMUNE DIABETIC NOD MICE.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S283
Author(s):  
Zhiguang Guo ◽  
Tao Wu ◽  
Alison M. Trexler ◽  
Sameer Nevile ◽  
Nicole Kirchhof ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Survival ◽  
Nod Mice ◽  
Islet Graft ◽  
Effect Of Therapy

scholarly journals Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Survival ◽  
Tolerance Induction ◽  
Nod Mice ◽  
Disease Recurrence ◽  
Nod Mouse ◽  
Islet Graft ◽  
Specific Effector ◽  
Syngeneic Islet Transplantation ◽  
Specific Tolerance

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4<sup>+</sup> T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

scholarly journals Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.

1998 ◽  
Vol 102 (10) ◽  
pp. 1807-1814 ◽  
Author(s):  
H Yasuda ◽  
M Nagata ◽  
K Arisawa ◽  
R Yoshida ◽  
K Fujihira ◽  
...  
Keyword(s):  
Graft Survival ◽  
Nod Mice ◽  
Islet Graft ◽  
Local Expression

scholarly journals Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

Diabetes ◽  
2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Survival ◽  
Tolerance Induction ◽  
Nod Mice ◽  
Disease Recurrence ◽  
Nod Mouse ◽  
Islet Graft ◽  
Specific Effector ◽  
Syngeneic Islet Transplantation ◽  
Specific Tolerance

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4+ T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4+ and CD8+ T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

Endogenous Expansion of Regulatory T Cells Leads to Long-Term Islet Graft Survival in Diabetic NOD Mice

2012 ◽  
Vol 12 (5) ◽  
pp. 1124-1132 ◽  
Author(s):  
Q. Shi ◽  
J. R. Lees ◽  
D. W. Scott ◽  
D. L. Farber ◽  
S. T. Bartlett
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Graft Survival ◽  
Nod Mice ◽  
Islet Graft
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