Depletion of CD25^+CD4^+T cells (Tregs) enhances the HBV-specific CD8^+ T cell response primed by DNA immunization

查看全文 作　　者：Yoshihiro [1]Furuichi;Hirotake [1]Tokuyama;Satoshi [2]Ueha;Makoto [3]Kurachi;Fuminori [1]Moriyasu;Kazuhiro [3]Kakimi

机构地区：[1]Fourth Department of Internal Medicine (Gastroenterology and Hepatology);[2]Department of Molecular and Preventive Medicine;[3]Department of Immunotherapeutics (Medinet)

出　　处：《World Journal of Gastroenterology》索引2005年第11卷第24期,共6页

基　　金：Supported by in part Grant-in-Aid for Scientific Research (C) (toK.K) 摘　　要：AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T ceils in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining.RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBVspecific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n = 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells.CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T ceil response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects. 关键词：CD25^+CD4^+T细胞 CD8^+T细胞乙型肝炎病毒 DNA 免疫机制

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Depletion of CD25^+CD4^+T cells (Tregs) enhances the HBV-specific CD8^+ T cell response primed by DNA immunization

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