The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion
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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Published: |
Frontiers Media
2017
|
| Online Access: | https://eprints.nottingham.ac.uk/45334/ |
| _version_ | 1848797111086219264 |
|---|---|
| author | Sachdev, Divya Gough, Kevin C. Flynn, Robin J. |
| author_facet | Sachdev, Divya Gough, Kevin C. Flynn, Robin J. |
| author_sort | Sachdev, Divya |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:58:41Z |
| format | Article |
| id | nottingham-45334 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:58:41Z |
| publishDate | 2017 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-453342020-05-04T19:01:45Z https://eprints.nottingham.ac.uk/45334/ The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion Sachdev, Divya Gough, Kevin C. Flynn, Robin J. 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. Frontiers Media 2017-08-21 Article PeerReviewed Sachdev, Divya, Gough, Kevin C. and Flynn, Robin J. (2017) The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion. Frontiers in Immunology, 8 . 1002/1-1002/10. ISSN 1664-3224 http://journal.frontiersin.org/article/10.3389/fimmu.2017.01002/full doi:10.3389/fimmu.2017.01002 doi:10.3389/fimmu.2017.01002 |
| spellingShingle | Sachdev, Divya Gough, Kevin C. Flynn, Robin J. The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title | The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title_full | The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title_fullStr | The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title_full_unstemmed | The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title_short | The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion |
| title_sort | chronic stages of bovine fasciola hepatica are dominated by cd4 t-cell exhaustion |
| url | https://eprints.nottingham.ac.uk/45334/ https://eprints.nottingham.ac.uk/45334/ https://eprints.nottingham.ac.uk/45334/ |