Li Yuan, Wang Xu, Douglas Steven D, Metzger David S, Woody George, Zhang Ting, Song Li, Ho Wen-Zhe
Division of Allergy and Immunology, Department of Pediatrics, Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
J Infect Dis. 2005 Sep 15;192(6):1093-101. doi: 10.1086/432957. Epub 2005 Aug 10.
We investigated the ability of CD8+ T cells to inhibit hepatitis C virus (HCV) replication in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from 11 of 20 HCV-infected subjects had no detectable HCV RNA. Removal of CD8+ T cells from these PBMCs resulted in detection of HCV RNA, and depletion of CD8+ T cells from PBMCs that had detectable HCV RNA amplified HCV replication. Reconstitution of CD8- PBMCs with autologous CD8+ T cells led to inhibition of HCV replication. Interferon-gamma produced by CD8+ T cells was partially responsible for CD8+ T cell-mediated noncytotoxic anti-HCV activity in PBMCs. This noncytotoxic anti-HCV activity was confirmed in HCV replicon cells. Supernatants from CD8+ T cell cultures inhibited HCV RNA expression in the replicon cells. These findings may have important implications for the immunopathogenesis of HCV in both immune and hepatic cells and are relevant to the development of host innate immunity-based anti-HCV interventions.
我们研究了CD8 + T细胞抑制外周血单个核细胞(PBMC)中丙型肝炎病毒(HCV)复制的能力。从20名HCV感染受试者中的11名分离出的PBMC未检测到HCV RNA。从这些PBMC中去除CD8 + T细胞导致检测到HCV RNA,并且从具有可检测到的HCV RNA的PBMC中耗尽CD8 + T细胞会增强HCV复制。用自体CD8 + T细胞重建CD8 - PBMC导致HCV复制受到抑制。CD8 + T细胞产生的干扰素 - γ部分负责PBMC中CD8 + T细胞介导的非细胞毒性抗HCV活性。这种非细胞毒性抗HCV活性在HCV复制子细胞中得到证实。CD8 + T细胞培养物的上清液抑制复制子细胞中的HCV RNA表达。这些发现可能对HCV在免疫细胞和肝细胞中的免疫发病机制具有重要意义,并且与基于宿主先天免疫的抗HCV干预措施的开发相关。