The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion



Sachdev, Divya, Gough, Kevin C and Flynn, Robin J ORCID: 0000-0001-5304-3088
(2017) The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion. FRONTIERS IN IMMUNOLOGY, 8 (AUG). 1002-.

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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.

Item Type: Article
Uncontrolled Keywords: Fasciola hepatica, chronic helminth infection, T-cell responses, IL-10, IL-2, hyporesponsive, anergy, Foxp3
Depositing User: Symplectic Admin
Date Deposited: 04 Sep 2017 15:13
Last Modified: 19 Jan 2023 06:56
DOI: 10.3389/fimmu.2017.01002
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3009295