Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization
Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization
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DOI：
10.3748/wjg.v11.i24.3772
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发表时间：
2005-06-28
影响因子：
4.3
通讯作者：
Kakimi, Kazuhiro
中科院分区：
文献类型：
--
作者：
Furuichi, Yoshihiro;Tokuyama, Hirotake;Kakimi, Kazuhiro
目的：持续性B型肝炎病毒（HBV）感染的特征是CD 8（+）T细胞对HBV的应答较弱。免疫策略，克服耐受性和提高这些次优反应可能有助于清除病毒在慢性感染的个人。因此，我们研究了CD 25（+）CD 4（+）调节性T（Treg）细胞是否可能参与抑制CD 8（+）T细胞引发或调节DNA免疫引发的抗病毒CD 8（+）T细胞应答的“峰值”大小。小鼠在DNA免疫前3天接受500 μ g抗CD 25 mAb腹腔注射，以消耗CD 25（+）细胞。结果：DNA免疫诱导了HBV特异性CD 8（+）T细胞的产生，并通过细胞内IFN-γ染色检测了CD 8（+）T细胞的功能。在T细胞应答高峰期（第10天），DNA免疫后7.1 +/-2.0%CD8（+）T细胞是HBV特异性的，而Treg缺失小鼠中12.7 +/-3.2%CD8（+）T细胞是HBV特异性的，这表明在缺乏CD 25（+）Treg细胞的情况下，DNA免疫诱导了更多抗原特异性CD 8（+）T细胞（n = 6，P
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 mu g of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25(+) cells. Induction of HBV-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-gamma 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