Center of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
Viral Immunol. 2010 Feb;23(1):63-70. doi: 10.1089/vim.2009.0061.
The roles of regulatory T cells (Tregs) and PD-1 in hepatitis B have not been clearly described. Also, the role of B and T lymphocyte attenuator (BTLA), which serves as a negative regulator of T-cell activation, is still unknown in hepatitis B. In this study, we analyzed the frequency of circulating CD4(+)CD25(high) Tregs in patients with chronic hepatitis B (CHB), and subsequently investigated expression of PD-1 and BTLA on CD4(+) T cells, as well as their relationships with the clinical index of CHB patients. A total of 39 CHB patients and 19 healthy persons as controls were enrolled in the study. We found that the frequency of CD4(+)CD25(high) Tregs and PD-1 expression on CD4(+) T cells was significantly increased in CHB patients compared with normal controls. However, BTLA expression on CD4(+) T cells showed no significant difference between the two groups. The frequency of Tregs was significantly higher in patients with HBV DNA titers >or=10(8) than in those with HBV DNA titers <10(8). Circulating CD4(+)CD25(high) Treg frequency and PD-1 expression on CD4(+) T cells correlated positively with serum HBV DNA load in CHB patients. Our findings suggest that the increased frequency of CD4(+)CD25(high) Tregs and PD-1 expression on CD4(+) T lymphocytes may inhibit the cellular immune response against HBV and affect viral clearance, leading to the persistence of chronic HBV infection.
调节性 T 细胞（Tregs）和 PD-1 在乙型肝炎中的作用尚未明确。此外，B 和 T 淋巴细胞衰减因子（BTLA）作为 T 细胞活化的负调节剂，其在乙型肝炎中的作用仍不清楚。在本研究中，我们分析了慢性乙型肝炎（CHB）患者循环 CD4+CD25+高 Tregs 的频率，并随后研究了 PD-1 和 BTLA 在 CD4+T 细胞上的表达及其与 CHB 患者临床指标的关系。共纳入 39 例 CHB 患者和 19 名健康对照者。我们发现，与正常对照组相比，CHB 患者 CD4+CD25+高 Tregs 和 CD4+T 细胞上 PD-1 的表达频率显著增加。然而，两组间 CD4+T 细胞上 BTLA 的表达无显著差异。HBV DNA 载量≥10^8 拷贝/ml 的患者 Tregs 的频率显著高于 HBV DNA 载量<10^8 拷贝/ml 的患者。CHB 患者循环 CD4+CD25+高 Treg 频率和 CD4+T 细胞上 PD-1 的表达与血清 HBV DNA 负荷呈正相关。我们的研究结果表明，CD4+CD25+高 Tregs 频率的增加和 CD4+T 淋巴细胞上 PD-1 的表达可能抑制了针对 HBV 的细胞免疫反应，并影响了病毒清除，导致慢性 HBV 感染的持续存在。
