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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fimmu-08-01002.pdf - Published version Download (2MB) |
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 |
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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 |