Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B1
Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B1
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DOI：
10.4049/jimmunol.177.1.739
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Wang, Fu-Sheng
中科院分区：
文献类型：
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作者：
Xu, Dongping;Fu, Junliang;Wang, Fu-Sheng
CD4(+)CD25（+）调节性T细胞（Treg）已被证明可以维持对自身和外源Ags的免疫耐受，但它们在持续性病毒感染中的作用尚未明确。在这项研究中，我们研究了CD4(+)CD25(+) Treg是否以及在何处促进慢性乙型肝炎（CHB）的发展。121例患者入组，其中急性乙型肝炎16例，慢性乙型肝炎76例，慢性重型乙型肝炎29例。我们发现慢性重型乙型肝炎患者的PBMC和肝脏浸润淋巴细胞CD4(+)CD25(+) Treg的频率显著升高，肝脏中FoxP3（+）细胞和炎症细胞浸润明显增加。在慢性乙型肝炎患者中，循环CD4(+)CD25(+) Treg频率与血清病毒载量显著相关。在急性乙型肝炎患者中，循环CD4(+)CD25(+) Treg频率最初较低，随着时间的推移，情况发生逆转，在恢复期循环Treg数量增加，并在消退后恢复到正常水平。在取自感染患者的PBMC中，CD4(+)CD25(+) Treg的消耗导致hbv - ag刺激的PBMC产生ifn - γ的增加。此外，CD4(+)CD25(+) Treg能够抑制HBV Ags介导的自体PBMC的增殖，这可能反映了HBV感染患者循环和肝脏中HBV- ag特异性Treg的产生。总之，我们的研究结果表明，CD4(+)CD25(+) Treg不仅在调节HBV感染的免疫应答效应中发挥积极作用，而且还影响乙型肝炎患者的疾病预后。
CD4(+)CD25(+) regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4(+)CD25(+) Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4(+)CD25(+) Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3(+)-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4(+)CD25(+) Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4(+)CD25(+) Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4(+)CD25(+) Treg led to an increase of IFN-gamma production by HBV-Ag-stimulated PBMC. In addition, CD4(+)CD25(+) Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4(+)CD25(+) Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.