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

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

doi:10.3389/fimmu.2017.01002

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, Article 1002. 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	https://nottingham-repository.worktribe.com/output/878672
Publisher URL	http://journal.frontiersin.org/article/10.3389/fimmu.2017.01002/full
Contract Date	Aug 31, 2017