Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Scand J Immunol. 2012 Sep;76(3):294-305. doi: 10.1111/j.1365-3083.2012.02725.x.
The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co-infection and 24 healthy individuals. CD4⁺ and CD8⁺ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4⁺ and CD8⁺ Tregs was found in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P < 0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with healthy controls (P < 0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4⁺ Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono-infected and HIV/HCV co-infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8⁺ Tregs and intrahepatic inflammation. In conclusion, HCV mono-infected patients and particularly HIV/HCV co-infected patients have increased the frequency of CD4⁺ and CD8⁺ Tregs compared with healthy controls. Furthermore, CD4⁺ Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection.
本研究旨在检测慢性丙型肝炎病毒（HCV）单感染和 HIV/HCV 共感染患者外周血和肝组织中的调节性 T 细胞（Tregs）。在一项横断面研究中，纳入了 51 例慢性 HCV 感染患者、24 例 HIV/HCV 共感染患者和 24 例健康对照者。采用流式细胞术检测 CD4+和 CD8+Tregs。通过瞬时弹性成像检查纤维化。对 12 例患者的肝活检标本进行炎症、纤维化和 Tregs 检测。与 HCV 单感染患者相比，HIV/HCV 共感染患者的 CD4+和 CD8+Tregs 频率增加[中位数：6.4%（IQR：5.7-6.9）和 1.0%（0.7-1.2），分别]（P=0.01 和 P＜0.001）。此外，HCV 单感染患者的 Tregs 频率高于健康对照者（P＜0.05）。然而，未发现 Tregs 频率与纤维化之间存在关联。此外，使用 CD45RA 对 CD4+Tregs 进行特征分析表明，与健康对照组相比，HCV 单感染和 HIV/HCV 共感染患者的活化 Tregs 频率更高。最后，肝内 Tregs 数量与外周血 CD8+Tregs 和肝内炎症均相关。结论：与健康对照组相比，HCV 单感染患者和特别是 HIV/HCV 共感染患者的 CD4+和 CD8+Tregs 频率增加。此外，感染患者的 CD4+Tregs 呈活化表型。Tregs 与纤维化无关，但发现肝内 Tregs 与炎症之间存在正相关。综上所述，这些结果表明 Tregs 在慢性 HCV 感染的发病机制中起作用。
