%A Sachdev,Divya %A Gough,Kevin C. %A Flynn,Robin J. %D 2017 %J Frontiers in Immunology %C %F %G English %K Fasciola hepatica,chronic helminth,CD4 T-cells,IL-10,IL-2,hyposresponsive,anergy,Foxp3 %Q %R 10.3389/fimmu.2017.01002 %W %L %M %P %7 %8 2017-August-21 %9 Original Research %+ Dr Robin J. Flynn,Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool,United Kingdom,rflynn@hiberniacollege.net %# %! Anergic T-cells during F. hepatica infection %* %< %T The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion %U https://www.frontiersin.org/articles/10.3389/fimmu.2017.01002 %V 8 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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.