Islet cell autoantigens in insulin-dependent diabetes.

Atkinson, Mark A.; Maclaren, Noel K.

doi:10.1172/jci116745

Cited by 127 publications

(64 citation statements)

References 67 publications

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“…RNA from the splenocytes of agematched and sex-matched NOD mice was used as a control. Two µg of total RNA was converted to cDNA using Superscript II reverse transcriptase (Gibco BRL, Gaithersburg, Md., USA) and oligo (dT) [12][13][14][15][16][17][18] . PCR was carried out using specific primers for various cytokine genes, as described previously [30].…”

Section: Construction Of Recombinant Vaccinia Virus Expressing Mouse mentioning

confidence: 99%

“…Therefore, various strategies, particularly autoantigen-based strategies, have been used to tolerise these autoreactive T cells and prevent autoimmune Type I diabetes in NOD mice. In NOD mice and human Type I diabetes, glutamic acid decarboxylase (GAD) and insulin are known to be major betacell autoantigens that play an important role in the development of diabetes [13,14].…”

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

et al. 2002

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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)

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Section: Construction Of Recombinant Vaccinia Virus Expressing Mouse mentioning

confidence: 99%

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confidence: 99%

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

et al. 2002

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“…Islet cells have many similarities to neurons [30,31], one being their high energy dependence on mitochondrial oxphos [31]. In particular, beta cells require mitochondrial ATP to sustain the production and release of insulin [31][32][33][34].…”

Section: Critical Effects Of Oxidative Phosphorylation Deficiencymentioning

confidence: 99%

“…As mentioned, beta cells resemble neurons in many respects [30,31], including their strict dependence on oxphos and also the high content GABA of which they secrete via synapticlike microvesicles [35,36]. The increased ATP levels produced by accelerated oxphos in response to high blood glucose levels not only promote insulin release [32][33][34], but also facilitate the accumulation of GABA into synaptic-like microvesicles and its subsequent release within the islets [35,36].…”

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The GABA network and the pathogenesis of IDDM

Esposti

Mackay

1997

Diabetologia

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Functional tolerance for prevention of Type 1 diabetes

Baxter

Poulton

1998

Diabetes Metab. Rev.

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Islet cell antibodies predict insulin-dependent diabetes in united states school age children as powerfully as in unaffected relatives. J Clin invest 93: 2403-2407, 1994. 8. Levy-Marchal C, Dubois F, Noel M, Tichet J, and Czernichow P: Immunogenetic determinants and prediction of IDDM in French schoolchildren. Diabetes 44: 1029-1032, 1995. 9. Hagopian WA, Sanjeevi CB, Kockum I, Landin Olsson M, Karlsen AE, Sundkvist G, Dahlquist G, Palmer J, and Lernmark A: Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J Clin Invest 95: 1505-1511, 1995.Immunological tolerance is defined as the antigen-specific absence of an immune

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Islet cell autoantigens in insulin-dependent diabetes.

Cited by 127 publications

References 67 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

The GABA network and the pathogenesis of IDDM

Functional tolerance for prevention of Type 1 diabetes

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