CD4+ T cell restoration and control of hepatitis C virus replication after childbirth
Samantha L. Coss, … , Christopher M. Walker, Jonathan R. Honegger
Samantha L. Coss, … , Christopher M. Walker, Jonathan R. Honegger
Published January 6, 2020
Citation Information: J Clin Invest. 2020;130(2):748-753. https://doi.org/10.1172/JCI123623.
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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

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Figure 3

Tetramer-positive CD4+ T cell phenotypes of 6 women with postpartum viral control.

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Tetramer-positive CD4+ T cell phenotypes of 6 women with postpartum vira...
(A) The viral load (column 1), tetramer-positive CD4+ T cell frequency (column 2), and phenotypic marker expression of tetramer-positive (black) and bulk (gray) CD4+ T cells (columns 3–5). All phenotypic analyses were performed at the 3PP time point, when tetramer-positive frequencies were highest. Relevant HLA alleles for class II tetramer studies are listed in the right column. (B) Spearman’s correlation of the change in viral load from T3 to 3PP with the frequency of tetramer-positive CD4+ T cells expressing PD-1 (left), CTLA-4 (middle), and PD-1 but not CTLA-4 (right) at 3PP.