T cell restoration and control of hepatitis C virus replication after childbirth

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.sup.+] 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.sup.+] T cell immunity. Class II tetramer analysis revealed significantly greater frequencies of circulating HCV-specific [CD4.sup.+] T cells at 3 months postpartum in women with concurrent declines in viremia compared with those with stable viremia. These HCV-specific [CD4.sup.+] T cells had an effector-memory phenotype. Inhibitory coreceptor expression on these cells corresponded to the degree of viral control. Circulating [CD4.sup.+] T cells produced IL-2 and IFN-[[gamma]] after HCV antigen stimulation, demonstrating Th1 functionality. These data provide direct evidence that the profound loss of HCV-specific [CD4.sup.+] T cell help that results in chronic infection is reversible following pregnancy, and this recovery of [CD4.sup.+] T cells is associated with at least transient control of persistent viral replication.
Introduction Hepatitis C virus (HCV) infections persist indefinitely in approximately three-quarters of infected individuals, predisposing to late complications, including hepatic cirrhosis and hepatocellular carcinoma (1). One of the strongest predictors [...]