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CD4+ T cell restoration and control of hepatitis C virus replication after childbirth.


ABSTRACT: 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-? 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.

SUBMITTER: Coss SL 

PROVIDER: S-EPMC6994162 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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CD4+ T cell restoration and control of hepatitis C virus replication after childbirth.

Coss Samantha L SL   Torres-Cornejo Almudena A   Prasad Mona R MR   Moore-Clingenpeel Melissa M   Grakoui Arash A   Lauer Georg M GM   Walker Christopher M CM   Honegger Jonathan R JR  

The Journal of clinical investigation 20200201 2


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 frequenc  ...[more]

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