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

Sachdev, Divya; Gough, Kevin C.; Flynn, Robin J.

Authors

Divya Sachdev

Kevin C. Gough

Robin J. Flynn



Abstract

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.

Citation

Sachdev, D., Gough, K. C., & Flynn, R. J. (2017). The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion. Frontiers in Immunology, 8, https://doi.org/10.3389/fimmu.2017.01002

Journal Article Type Article
Acceptance Date Aug 4, 2017
Publication Date Aug 21, 2017
Deposit Date Aug 31, 2017
Publicly Available Date Aug 31, 2017
Journal Frontiers in Immunology
Electronic ISSN 1664-3224
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 8
Article Number 1002
DOI https://doi.org/10.3389/fimmu.2017.01002
Public URL http://eprints.nottingham.ac.uk/id/eprint/45334
Publisher URL http://journal.frontiersin.org/article/10.3389/fimmu.2017.01002/full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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