| Autor: |
D. Loirat, M. Mancini-Bourgine, Abastado J.-P., Michel M.-L. |
| Předmět: |
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| Zdroj: |
International Immunology; 10/1/2003, Vol. 15 Issue 10, p1125, 12p |
| Abstrakt: |
A humanized murine model was developed to study T cell tolerance to the hepatitis B surface antigen (HBsAg) that is present in sera of hepatitis B virus chronic carriers. The HBsAg/HLA-A2 double-transgenic mice express a chimeric HLA-A2 MHC class I molecule and a high amount of the HBsAg in the liver that is secreted and present in sera during the animal's lifetime. In these mice, injection of plasmid DNA encoding HBsAg induced a high frequency of CD8+ T cells secreting IFN-γ in the periphery, with in vitro cytolytic activity and specificity for two dominant HBs-specific HLA-A2-restricted epitopes. Nevertheless, the DNA-based immunization elicited neither Th1 nor Th2 CD4+ T cell responses. Despite a high concentration of HBsAg in sera, these mice developed an immunocompetent CD8+ T cell repertoire towards the viral self-antigen, whereas the CD4+ T cell repertoire was tolerized. In the absence of a CD4+ T cell response, the IFN-γ-secreting CD8+ T cells primed by DNA-based immunization were unable to exert their antiviral functions in vivo on liver cells expressing the transgene product. However, when pro-inflammatory stimuli were given before or after DNA-based immunization, the HBsAg was cleared from the serum. This effect was antibody dependent and associated with the detection of an HBs-specific Th1 CD4+ T cell response in the periphery. This model provides evidence that HBsAg displayed a strong tolerogenic effect on the CD4+ T cell compartment that is associated with a defect in CD8+ T cell effector functions in vivo. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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