Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin

Carel, Jean‐Claude; Bougnères, Pierre; Vardi, Pnina

doi:10.1007/bf03347752

Cited by 125 publications

(157 citation statements)

References 40 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…In Type I diabetes, GAD and insulin have been identified as major autoantigens and tolerisation against these autoantigens has been attempted as a method for the prevention of the disease [14,32]. It has been reported that administration of purified GAD protein or peptide or insulin protein or peptide to NOD mice by a variety of routes can tolerise the T cell-mediated immune response against pancreatic beta cells, resulting in the prevention or delay of the development of insulitis and diabetes [28,29,33,34,35,36,37,38,39]. In many cases, the preventive effect was found to be associated with a Th2 shift [14,32].…”

Section: Discussionmentioning

confidence: 99%

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

et al. 2002

View full text Add to dashboard Cite

Aims/hypotheses. Type I (insulin-dependent) diabetes mellitus results from T-cell-mediated autoimmune destruction of pancreatic beta cells. Among the beta-cell autoantigens that have been implicated in triggering of beta-cell-specific autoimmunity, glutamic acid decarboxylase (GAD) is a strong candidate in both humans and the NOD mouse. We aimed to determine whether treatment with a recombinant vaccinia virus expressing GAD (rVV-GAD65) could prevent the development of diabetes in NOD mice. Methods. Three-eight-to-nine-week-old female NOD mice were injected with various doses of rVV-GAD65 or rVV-MJ601as a control. We then examined the incidence of diabetes, T-cell proliferative response to GAD, amounts of anti-GAD IgGs, cytokine production and generation of regulatory cell populations. Results. Administration of rVV-GAD65 to NOD mice prevented diabetes in an age-dependent and dose-dependent manner. Splenic T cells from rVV-GAD65-treated mice did not proliferate in response to GAD65.The amount of IgG1 was increased, whereas IgG2a amounts did not change in rVV-GAD65-treated NOD mice. The production of interleukin-4 increased, whereas the production of interferon-γ decreased in rVV-GAD65-treated mice after stimulation with GAD. Furthermore, splenocytes from rVV-GAD65-treated NOD mice prevented the transfer of diabetes by splenocytes from acutely diabetic NOD mice in NOD.scid recipients. Conclusion/interpretation. Immunogene therapy using a recombinant vaccinia virus expressing GAD results in the prevention of autoimmune diabetes in NOD mice by the induction of immunological tolerance through active suppression of effector T cells, and this treatment might have therapeutic value for the prevention of Type I diabetes. [Diabetologia (2002)

show abstract

Section: Discussionmentioning

confidence: 99%

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

et al. 2002

View full text Add to dashboard Cite

show abstract

“…These include islet-specific Ags, like insulin, and other nonislet-specific Ags, like glutamic acid decarboxylase (GAD) 3 65, carboxypeptidase H, and IA-2 among others (11,12). Of all the known autoantigens implicated in the disease process, treatment with only insulin, GAD 65, and the heat shock protein (hsp) 60 peptide p277 can protect nonobese diabetic (NOD) mice from disease (13)(14)(15)(16). Insulin and GAD 65 are also the most prominent islet autoantigens shown to be recognized by peripheral T cells from type 1 diabetes patients (17,18).…”

mentioning

confidence: 99%

Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model

Abraham

Marietta

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The genetic factors that contribute to the etiology of type 1 diabetes are still largely uncharacterized. However, the genes of the MHC (HLA in humans) have been consistently associated with susceptibility to disease. We have used several transgenic mice generated in our laboratory, bearing susceptible or resistant HLA alleles, in the absence of endogenous MHC class II (Aβo), to study immune responses to the autoantigen glutamic acid decarboxylase (GAD) 65 and its relevance in determining the association between autoreactivity and disease pathogenesis. Mice bearing diabetes-susceptible haplotypes, HLA DR3 (DRB1*0301) or DQ8 (DQB1*0302), singly or in combination showed spontaneous T cell reactivity to rat GAD 65, which is highly homologous to the self Ag, mouse GAD 65. The presence of diabetes-resistant or neutral alleles, such as HLA DQ6 (DQB1*0602) and DR2 (DRB1*1502) prevented the generation of any self-reactive responses to rat GAD. In addition, unmanipulated Aβo/DR3, Aβo/DQ8, and Aβo/DR3/DQ8 mice recognized specific peptides, mainly from the N-terminal region of the GAD 65 molecule. Most of these regions are conserved between human, mouse, and rat GAD 65. Further analysis revealed that the reactivity was mediated primarily by CD4+ T cells. Stimulation of these T cells by rat GAD 65 resulted in the generation of a mixed Th1/Th2 cytokine profile in the Aβo/DR3/DQ8, Aβo/DR3, and Aβo/DQ8 mice. Thus, the presence of diabetes-associated genes determines whether immune tolerance is maintained to islet autoantigens, but autoreactivity in itself is not sufficient to induce diabetes.

show abstract

“…Furthermore, treatment of prediabetic NOD mice with insulin (oral, subcutaneous, intranasal) [28][29][30] or GAD (intravenous, intrathymic, intranasal) [31][32][33], delays, or even prevents the onset of IDDM.…”

mentioning

confidence: 99%

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

et al. 1997

View full text Add to dashboard Cite

Insulin-dependent diabetes mellitus (IDDM) is the result of a genetically associated autoimmune mediated process in which the insulin-producing pancreatic beta-cells are thought to be destroyed by autoreactive T cells [1,2]. The disease process is accompanied by autoreactive T cells and autoantibodies to various islet antigens. Many IDDM patients develop humoral immune responses to insulin [3,4], islet cells [5], tyrosine phosphatase homologue islet cell antibody ((ICA)512/islet cell antigen (IA)-2, 37 K) [6-9] and glutamic acid decarboxylase (GAD)65 [10][11][12]. Even though autoantibodies may not be directly involved in the destructive process, 60 % of new-onset diabetic patients are positive for insulin autoantibodies (IAA) compared to only 0.5 % of healthy control subjects [2]. The involvement of T cells in the pathogenesis has been implicated by insulitis [13], the recurrence of insulitis and diabetes after pancreas transplantation [14] and the transfer of diabetes with non-T-cell-depleted bone marrow transplants

show abstract

Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin

Cited by 125 publications

References 40 publications

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

Contact Info

Product

Resources

About