The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion
Sachdev, Divya; Gough, Kevin C.; Flynn, Robin J.
Kevin C. Gough
Robin J. Flynn
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.
|Journal Article Type||Article|
|Publication Date||Aug 21, 2017|
|Journal||Frontiers in Immunology|
|Peer Reviewed||Peer Reviewed|
|APA6 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|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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