Methods: Cryopreserved peripheral blood mononuclear cells collected from HCV-infected women during and after pregnancy were thawed, stimulated with peptides corresponding to HCV NS3 and NS4 proteins, and analyzed for production of IFNγ, IL2, IL10, IL17a, and IL21 by intracellular cytokine staining and flow cytometry. Longitudinal HCV-specific T cell responses were compared between 6 women with ≥ 1 log10 declines in viral load between the 3rd trimester of pregnancy and 3 months postpartum and 12 women with < 1 log10 decline in viral load.
Results: Although the two groups of women exhibited similar T-cell responses in late pregnancy, at 3 months postpartum those women with significant postpartum viral declines had higher frequencies of HCV-specific IFNγ+ (p=0.047) and IFNγ+IL2+ co-producing CD4+ T-cells (p=0.041) than women with stable viremia. Postpartum viral control was also associated with greater increases in IFNγ+ CD4+ T-cell frequencies between late pregnancy and 3 months postpartum (median absolute increase: 0.04% versus 0.00%, p=0.018). For CD8+ T-cells, a trend toward greater HCV-specific IFNγ production at 3 months postpartum was detected among women with postpartum viral control (p=0.072). Virus-specific T cell production of IL10, IL17a, and IL21 was rare for both groups.
Conclusion: Women with postpartum viral load declines of at least 1 log10 demonstrated increased HCV-specific Th1 T cell responses at 3 months postpartum as compared to the 3rd trimester, and these increases were larger than those seen in women with stable viremia. These functional improvements correspond temporally with declines in viral load, suggesting that restoration of virus-specific Th1 function may contribute to the spontaneous control of HCV viral load in the postpartum period.