Coss Samantha L, Torres-Cornejo Almudena, Prasad Mona R, Moore-Clingenpeel Melissa, Grakoui Arash, Lauer Georg M, Walker Christopher M, Honegger Jonathan R
The Ohio State University College of Medicine, Columbus, Ohio, USA.
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
J Clin Invest. 2020 Feb 3;130(2):748-753. doi: 10.1172/JCI123623.
Chronic hepatitis C virus (HCV) infection is characterized by persistent high-level viremia and defective cellular immunity, including a lack of functional HCV-specific CD4+ T cells. We previously described an exceptional period of viral control that occurs in some chronically infected women after childbirth. Here, we investigated whether reduced HCV replication after pregnancy is associated with recovery of CD4+ T cell immunity. Class II tetramer analysis revealed significantly greater frequencies of circulating HCV-specific CD4+ T cells at 3 months postpartum in women with concurrent declines in viremia compared with those with stable viremia. These HCV-specific CD4+ T cells had an effector-memory phenotype. Inhibitory coreceptor expression on these cells corresponded to the degree of viral control. Circulating CD4+ T cells produced IL-2 and IFN-γ after HCV antigen stimulation, demonstrating Th1 functionality. These data provide direct evidence that the profound loss of HCV-specific CD4+ T cell help that results in chronic infection is reversible following pregnancy, and this recovery of CD4+ T cells is associated with at least transient control of persistent viral replication.
慢性丙型肝炎病毒（HCV）感染的特征是持续的高水平病毒血症和细胞免疫缺陷，包括缺乏功能性HCV特异性CD4 + T细胞。我们之前描述过，一些慢性感染的女性在产后会出现一段特殊的病毒控制期。在此，我们研究了妊娠后HCV复制减少是否与CD4 + T细胞免疫的恢复有关。II类四聚体分析显示，与病毒血症稳定的女性相比，病毒血症同时下降的女性在产后3个月时循环中HCV特异性CD4 + T细胞的频率显著更高。这些HCV特异性CD4 + T细胞具有效应记忆表型。这些细胞上抑制性共受体的表达与病毒控制程度相对应。循环中的CD4 + T细胞在HCV抗原刺激后产生IL-2和IFN-γ，表明具有Th1功能。这些数据提供了直接证据，表明导致慢性感染的HCV特异性CD4 + T细胞辅助功能的严重丧失在妊娠后是可逆的，并且CD4 + T细胞的这种恢复与持续性病毒复制的至少短暂控制有关。
