The chronic stages of Bovine Fasciola hepatica are Dominated by cD4 T-cell exhaustion

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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-ß 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 ?d (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-ß, 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.

Original languageEnglish
Article number1002
JournalFrontiers in Immunology
Volume8
Issue numberAUG
DOIs
Publication statusPublished - 21 Aug 2017
Externally publishedYes

Keywords

  • Anergy
  • Chronic helminth infection
  • Fasciola hepatica
  • Foxp3
  • Hyporesponsive
  • IL-10
  • IL-2
  • T-cell responses

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