Antigen Based Therapies to Prevent Diabetes in NOD Mice

Ramiya, Vijayakumar K.; Shang, Xiaozhou; Pharis, Peter G.; Wasserfall, Clive; Stäbler, Thomas; Muir, Andrew; Schatz, Desmond; Maclaren, Noel K.

doi:10.1006/jaut.1996.0047

Cited by 50 publications

(30 citation statements)

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“…Thus, a second interpretation of GAD65-induced IDDM modulation could be that the high dose of Ag used to stimulate the immune system prevents animals from becoming clinically diabetic in a manner independent of the specific determinant. Some researchers, for example, have found that whereas GAD peptide immunization could not prevent IDDM in NOD mice, diphtheria-tetanus toxoid-acellular pertussis alone or insulin B chain peptide could mitigate IDDM (16). Furthermore, recent work also suggests that intrathymic injection of NOD mice with whole pancreas tissue or insulin B chain peptides could prevent IDDM but that certain GAD peptides accelerate disease (17).…”

Section: T Ype I (Insulin-dependent) Diabetes Mellitus (Iddm)mentioning

confidence: 99%

“…As compared with offspring of NOD mothers treated midgestation with either a single control peptide (the IA g7 -binding HEL [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] or the nonbinding MBP 123-137 ) or a mixture of control peptides (PSA 95-109 plus MBP 123-137 ), offspring of mice given some GAD65 peptide treatment regimens clearly had a reduced incidence of IDDM (Fig. 2).…”

Section: Offspring Of Gad-treated Pregnant Nod Mice Display a Signifimentioning

confidence: 99%

“…with 50 g GAD65 246 -266 , GAD65 509 -528 , or GAD65 524 -543 (GAD65 p17, p34, or p35 single); 50 g of a mixture of GAD65 509 -528 plus 50 g GAD65 524 -543 (GAD65 p34 plus p35 mix); or 50 g of a mixture of GAD65 246 -266 , 50 g GAD65 509 -528, and 50 g GAD65 524 -543 (GAD65 p17 plus p34 plus p35 mix). Controls consisted of 50 g HEL [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] (control HEL single, a tight binding peptide to IA g7 that elicits a strong immune response), 50 g MBP 123-137 (control MBP single, which does not bind to IA g7 ) and a mixture of 50 g MBP 123-137 plus 50 g PSA 95-109 (control MBP plus PSA mix). After weaning, male NOD mice were culled, and female offspring mice were monitored for the development of hyperglycemia (see Materials and Methods).…”

Section: Offspring Of Gad-treated Pregnant Nod Mice Display a Signifimentioning

confidence: 99%

“…Stimulation index (SI) was calculated as the test counts divided by the background control standard (as defined in the text). [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] , an IA g7 -binding peptide known to produce proliferative responses in NOD mice. Injection groups 7 and 8 consisted of peptides unable to be bound by IA g7 .…”

Section: Proliferation Assaysmentioning

confidence: 99%

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Therapeutic Alteration of Insulin-Dependent Diabetes Mellitus Progression by T Cell Tolerance to Glutamic Acid Decarboxylase 65 Peptides In Vitro and In Vivo

Wilson

White

DeLuca

2001

The Journal of Immunology

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We have reported previously that nonobese diabetic (NOD) fetal pancreas organ cultures lose the ability to produce insulin when maintained in contact with NOD fetal thymus organ cultures (FTOC). Initial studies indicated that exposure to glutamic acid decarboxylase (GAD65) peptides in utero resulted in delay or transient protection from insulin-dependent diabetes mellitus (IDDM) in NOD mice. We also found that exposure of young adult NOD mice to the same peptides could result in acceleration of the disease. To more closely examine the effects of early and late exposure to diabetogenic Ags on T cells, we applied peptides derived from GAD65 (GAD AA 246–266, 509–528, and 524–543), to our “in vitro IDDM” (ivIDDM) model. T cells derived from NOD FTOC primed during the latter stages of organ culture, when mature T cell phenotypes are present, had the ability to proliferate to GAD peptides. ivIDDM was exacerbated under these conditions, suggesting that GAD responsiveness correlates with the ivIDDM phenotype, and parallels the acceleration of IDDM we had seen in young adult NOD mice. When GAD peptides were present during the initiation of FTOC, GAD proliferative responses were inhibited, and ivIDDM was reduced. This result suggests that tolerance to GAD peptides may reduce the production of diabetogenic T cells or their capacity to respond, as suggested by the in utero therapies studied in NOD mice.

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Section: T Ype I (Insulin-dependent) Diabetes Mellitus (Iddm)mentioning

confidence: 99%

Section: Offspring Of Gad-treated Pregnant Nod Mice Display a Signifimentioning

confidence: 99%

Section: Offspring Of Gad-treated Pregnant Nod Mice Display a Signifimentioning

confidence: 99%

Section: Proliferation Assaysmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic Alteration of Insulin-Dependent Diabetes Mellitus Progression by T Cell Tolerance to Glutamic Acid Decarboxylase 65 Peptides In Vitro and In Vivo

Wilson

White

DeLuca

2001

The Journal of Immunology

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“…Administration of autoantigens can be used for prevention of IDDM. Immunization of spontaneous NOD mice with cell autoantigen such as insulin and GAD prevented the development of IDDM [20,21]. These antigens appear to modulate the T-cell-mediated immune response through antigen-driven immunosuppression and then provide long-term protection from autoimmune destruction of cell.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protein as a New Autoantigen Reactive with Non-obese Diabetic Mice Sera

Choi

Kim

et al. 2000

Journal of Autoimmunity

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Deaggregated homologous immunoglobulin-peptide conjugates induce peptide-specific T cell nonresponsivenessin vivo

Seddon

Mason

1998

Eur. J. Immunol.

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Previous studies have proven the efficacy of intravenous injection of deaggregated protein as a means of inducing tolerance. In the present study, the immunodominant peptide 70-86 of myelin basic protein (MBP) was covalently linked to either mouse Ig or Lewis rat IgG. Lewis rats immunized with MBP in complete Freund's adjuvant were completely protected from development of experimental allergic encephalomyelitis (EAE) by their injection with as little as 40 ? g of peptide conjugate on days 0 and 10 after immunization. Peptide-specific proliferative and cytokine responses by T cells from treated rats in vitro were severely depressed compared with controls, while responses to whole MBP were unaffected. Significantly , injections of 100 ? g of peptide conjugate on days 0 and 4 after adoptive transfer of peptide-specific T lines protected rats from passive EAE while a single injection of 100 ? g of conjugate at the onset of active EAE prevented any further disease progression. Both results suggest that primed effector cells as well as naive T cells are prone to tolerance induction by this means. The ability to intervene in ongoing immune responses with such specificity may be useful therapeutically in control of autoimmunity or allergic responses to environmental antigens.

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Antigen Based Therapies to Prevent Diabetes in NOD Mice

Cited by 50 publications

References 0 publications

Therapeutic Alteration of Insulin-Dependent Diabetes Mellitus Progression by T Cell Tolerance to Glutamic Acid Decarboxylase 65 Peptides In Vitro and In Vivo

Therapeutic Alteration of Insulin-Dependent Diabetes Mellitus Progression by T Cell Tolerance to Glutamic Acid Decarboxylase 65 Peptides In Vitro and In Vivo

Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protein as a New Autoantigen Reactive with Non-obese Diabetic Mice Sera

Deaggregated homologous immunoglobulin-peptide conjugates induce peptide-specific T cell nonresponsivenessin vivo

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