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Viral hepatitis
PMO-152 Characterising the immune status of HBV-specific CD4+ and CD8+ T-cells producing IL-17 in patients with chronic hepatitis B (CHB) virus infection
  1. H Cooksley1,
  2. A Riva1,
  3. M Simonova2,
  4. K Katzarov2,
  5. S Chokshi1
  1. 1Institute of Hepatology, Foundation for Liver Research, London, UK
  2. 2Clinic of Gastroenterology & Hepatology, Military Medical Academy, Sofia, Bulgaria

Abstract

Introduction Virus specific CD4+ and CD8+T-cells are essential in the control of HBV infection and their functions are tightly regulated by immune homeostatic control mechanisms, such as the programmed death (PD1) pathway, Tim3 and CD244. These pathways maintain the equilibrium between efficient control of viral replication and unnecessary inflammatory/immunopathological damage. Recent studies have described a unique subset of T-cells which produce IL-17. Preliminary studies suggest that IL-17-producing T-cells maybe involved in inflammation and liver damage but largely the role of HBV-specific IL-17 producing CD4+(Th17) and CD8+(Tc17) T-cells during chronic HBV infection remains elusive. Moreover, the impact of immunoregulatory signatures on these T-cells are unknown. The aim of this study was to characterise the role and immune status of virus-specific CD4+ Th17 and CD8+ Tc17 cells in CHB patients.

Methods Peripheral blood mononuclear cells were collected from ten treatment naïve HBeAg+ CHB patients and ten healthy controls. PBMC's were stimulated with recombinant HBcAg/HBsAg and PMA/Ionomycin. The frequency of total and virus-specific CD4 and CD8 T-cell producing IL-17/IFNg and the expression of T-cell immunoregulatory molecules PD1, Tim3 and CD244 was analysed by flow cytometry.

Results Total number of CD8+ T-cells producing IL-17 was not different between chronic HBV patients and healthy controls. However HBV-specific Tc17 cells were significantly higher in CHB-patients compared to controls (p=0.007). Total Th17 were also higher in CHB-patients compared to controls (p=0.03) however the difference was more pronounced in HBV-specific CD4+ Th-17 (p=0.003). Upon analysis of the immune-homeostatsis signatures we found a higher expression of PD1 and CD244 on HBV-specific CD4+ and CD8+ T-cells producing IFNg (p<0.001 and p=0.026 respectively) in CHB patients. No expression of Tim3 was found on these cells. However, HBV-specific Th17 cells in the CHB patients did not express PD1 or CD244 but had levels of Tim3 significantly lower than healthy controls (p=0.027).

Conclusion This study reveals the involvement of virus-specific Th17 and Tc17 in the pathogenesis of chronic HBV infection. Interestingly, we observe differential patterns of immunoregulatory signatures operational within the populations of virus-specific T-cells producing IFNg and IL-17 which may influence their role in HBV disease.

Competing interests None declared.

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