The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion

Sachdev, Divya and Gough, Kevin C. and Flynn, Robin J. (2017) The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion. Frontiers in Immunology, 8 . 1002/1-1002/10. ISSN 1664-3224

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Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1+) population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN) characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
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Depositing User: Eprints, Support
Date Deposited: 31 Aug 2017 13:12
Last Modified: 04 May 2020 19:01

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