Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsKumashie, Kingsley Gideon
Pils, Marina C
MetadataShow full item record
AbstractChronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.
CitationFront Immunol. 2021 Feb 3;11:592328. doi: 10.3389/fimmu.2020.592328.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
JournalFrontiers in immunology
The following license files are associated with this item:
- Creative Commons
- Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection.
- Authors: He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L
- Issue date: 2016 Aug 2
- Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.
- Authors: Ochel A, Cebula M, Riehn M, Hillebrand U, Lipps C, Schirmbeck R, Hauser H, Wirth D
- Issue date: 2016 Nov
- TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall.
- Authors: Cebula M, Riehn M, Hillebrand U, Kratzer RF, Kreppel F, Koutsoumpli G, Daemen T, Hauser H, Wirth D
- Issue date: 2017 Oct 4
- CD8<sup>+</sup> T cell exhaustion.
- Authors: Kurachi M
- Issue date: 2019 May
- The elusive identity of CXCR5<sup>+</sup> CD8 T cells in viral infection and autoimmunity: Cytotoxic, regulatory, or helper cells?
- Authors: Fousteri G, Kuka M
- Issue date: 2020 Mar