尽管丙型肝炎病毒（HCV）/艾滋病病毒（HIV）合并感染中CD4+T细胞整体减少，但肝内HCV特异性CD4+T细胞反应仍得以保留。

Preservation of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses despite global loss of CD4+ T cells in HCV/HIV coinfection.

作者信息

Morishima Chihiro, Shuhart Margaret C, Yoshihara Christina S, Paschal Denise M, Silva Melissa A, Thomassen Lisa V, Emerson Scott S, Gretch David R

机构信息

Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.

出版信息

J Infect Dis. 2007 Aug 15;196(4):577-86. doi: 10.1086/519386. Epub 2007 Jun 28.

DOI:10.1086/519386

PMID:17624844

Abstract

BACKGROUND

Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4(+) T cell counts are associated with increased hepatitis C liver disease.

METHODS

Hepatitis C virus (HCV)-specific CD4(+) T cell responses were assessed using interferon (IFN)- gamma enzyme-linked immunospot assays on peripheral blood mononuclear cells and expanded liver lymphocytes from HCV-monoinfected and HCV/HIV-coinfected subjects. Cell frequencies were determined using flow cytometry.

RESULTS

HIV coinfection was associated with decreased CD4(+) T cell percentages in both peripheral blood (21% vs. 48%; P<.0001) and liver (15% vs. 36%; P<.0001) and with reduced responsiveness of peripheral CD4(+) T cells to HCV antigens compared with HCV monoinfection (22% vs. 45%; P=.021). However, intrahepatic HCV-specific responses were maintained in HCV/HIV coinfection, compared with HCV monoinfection (38% vs. 32%; P=.7). Notably, the presence of HCV-specific responses was not related to the frequency of liver CD4(+) T cells (P=.4). Circulating and liver CD4(+) T cell percentages were correlated (r=0.58; P<.0001). Circulating percentages were also inversely associated with liver fibrosis stage among HCV/HIV-coinfected subjects (P=.029). Neither hepatic CD4(+) T cell percentages nor HCV-specific IFN- gamma responses in the liver or periphery predicted stage.

CONCLUSIONS

Despite decreases in peripheral blood HCV-specific CD4(+) T cell responses and intrahepatic CD4(+) T cell percentages, intrahepatic HCV-specific CD4(+) IFN- gamma responses were preserved in HCV/HIV coinfection.

摘要

背景

人类免疫缺陷病毒（HIV）合并感染及外周血CD4(+) T细胞计数降低与丙型肝炎肝脏疾病的加重相关。

方法

采用干扰素（IFN）-γ酶联免疫斑点试验，对外周血单个核细胞以及来自丙型肝炎病毒（HCV）单一感染和HCV/HIV合并感染受试者的肝脏淋巴细胞进行检测，以评估HCV特异性CD4(+) T细胞反应。通过流式细胞术确定细胞频率。

结果

与HCV单一感染相比，HIV合并感染与外周血（21%对48%；P<0.0001）和肝脏（15%对36%；P<0.0001）中CD4(+) T细胞百分比降低以及外周CD4(+) T细胞对HCV抗原的反应性降低相关（22%对45%；P = 0.021）。然而，与HCV单一感染相比，HCV/HIV合并感染时肝内HCV特异性反应得以维持（38%对32%；P = 0.7）。值得注意的是，HCV特异性反应的存在与肝脏CD4(+) T细胞频率无关（P = 0.4）。循环和肝脏CD4(+) T细胞百分比具有相关性（r = 0.58；P<0.0001）。在HCV/HIV合并感染受试者中，循环百分比也与肝纤维化分期呈负相关（P = 0.029）。肝脏CD4(+) T细胞百分比以及肝脏或外周的HCV特异性IFN-γ反应均不能预测分期。