Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase.
Diabetologia
; 45(5): 668-76, 2002 May.
Article
en En
| MEDLINE
| ID: mdl-12107747
ABSTRACT
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-gamma 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Vacunas de ADN
/
Traslado Adoptivo
/
Diabetes Mellitus Tipo 1
/
Glutamato Descarboxilasa
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Isoenzimas
Límite:
Animals
Idioma:
En
Revista:
Diabetologia
Año:
2002
Tipo del documento:
Article
País de afiliación:
Canadá