CD4+ T cell restoration and control of hepatitis C virus replication after childbirth
Samantha L. Coss, Almudena Torres-Cornejo, Mona R. Prasad, Melissa Moore-Clingenpeel, Arash Grakoui, Georg M. Lauer, Christopher M. Walker, Jonathan R. Honegger
Samantha L. Coss, Almudena Torres-Cornejo, Mona R. Prasad, Melissa Moore-Clingenpeel, Arash Grakoui, Georg M. Lauer, Christopher M. Walker, Jonathan R. Honegger
View: Text | PDF
Concise Communication Immunology Infectious disease

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-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.

Authors

Samantha L. Coss, Almudena Torres-Cornejo, Mona R. Prasad, Melissa Moore-Clingenpeel, Arash Grakoui, Georg M. Lauer, Christopher M. Walker, Jonathan R. Honegger

×

Figure 1

Function of HCV-specific CD4+ T cells in women with and without postpartum viral control.

Options: View larger image (or click on image) Download as PowerPoint
Function of HCV-specific CD4+ T cells in women with and without postpart...
(A) Plasma HCV RNA levels at the third trimester (T3) and 3 months postpartum (3PP) for 10 women with (controllers) and 22 women without (noncontrollers) postpartum viral load reductions of at least 1 log10 IU/mL. (B) Example HCV-specific CD4+ T cell cytokine responses of 1 controller and 1 noncontroller assessed by intracellular cytokine stain following PBMC stimulation with 3 separate peptide pools spanning HCV NS3-NS4. (C) Background-subtracted frequencies of HCV-specific cytokine-producing CD4+ T cells at T3 and 3PP for 10 controllers (left) and 22 noncontrollers (right) (Wilcoxon matched-pairs signed rank test). (D) Pearson’s correlation of changes in viral load and HCV-specific IL-2+IFN-γ+ CD4+ T cell frequencies from T3 to 3PP. (E) HCV-specific CD4+ T cell IL-2+IFN-γ+ coproduction of controllers and noncontrollers at T3, 3PP, 6PP, and 12PP (Mann-Whitney U test). Horizontal lines indicate median values. *P < 0.05; **P < 0.01.