Distinct phenotype and function of circulating Vδ1+ and Vδ2+ γδT-cells in acute and chronic hepatitis B.

Authors:
Kyong-Mi Chang
Kyong-Mi Chang
University of Pennsylvania
United States
Daniel Traum
Daniel Traum
Columbia University College of Physicians & Surgeons
United States
Jang-June Park
Jang-June Park
Vanderbilt University School of Medicine
United States
Suzanne Ho
Suzanne Ho
The Chinese University of Hong Kong
Hong Kong
Keisuke Ojiro
Keisuke Ojiro
School of Medicine
Japan
David K Wong
David K Wong
University of Toronto
Canada
Abdus S Wahed
Abdus S Wahed
University of Pittsburgh
United States
Norah A Terrault
Norah A Terrault
University of California
United States

PLoS Pathog 2019 Apr 18;15(4):e1007715. Epub 2019 Apr 18.

Department of Internal Medicine, University of Michigan, Ann Arbor MI, United States of America.

Hepatitis B virus (HBV) persists with global and virus-specific T-cell dysfunction, without T-cell based correlates of outcomes. To determine if γδT-cells are altered in HBV infection relative to clinical status, we examined the frequency, phenotype and function of peripheral blood Vδ1+ and Vδ2+γδT-cells by multi-parameter cytometry in a clinically diverse North American cohort of chronic hepatitis B (CHB), acute hepatitis B (AHB) and uninfected control subjects. We show that circulating γδT-cells were comprised predominantly of CD3hiCD4- Vδ2+γδT-cells with frequencies that were 2-3 fold higher among Asian than non-Asian Americans and inversely correlated with age, but without differences between CHB, AHB and control subjects. However, compared to control subjects, CHB was associated with increased TbethiEomesdim phenotype in Vδ2+γδT-cells whereas AHB was associated with increased TbethiEomesdim phenotype in Vδ1+γδT-cells, with significant correlations between Tbet/Eomes expression in γδT-cells with their expression of NK and T-cell activation and regulatory markers. As for effector functions, IFNγ/TNF responses to phosphoantigens or PMA/Ionomycin in Vδ2+γδT-cells were weaker in AHB but preserved in CHB, without significant differences for Vδ1+γδT-cells. Furthermore, early IFNγ/TNF responses in Vδ2+ γδT-cells to brief PMA/Ionomycin stimulation correlated inversely with serum ALT but not HBV DNA. Accordingly, IFNγ/TNF responses in Vδ2+γδT-cells were weaker in patients with CHB with hepatitis flare compared to those without hepatitis flares, and this functional deficit persisted beyond clinical resolution of CHB flare. We conclude that circulating γδT-cells show distinct activation and differentiatiation in acute and chronic HBV infection as part of lymphoid stress surveillance with potential role in clinical outcomes.

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http://dx.doi.org/10.1371/journal.ppat.1007715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490945PMC
April 2019
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