HBV Infection: Host's CD8+T Lymphocytic Responses And Clinical Outcomes

[Objective]:The pathogenesis of HBV infection has not been well elucidated.Our study aims to analyse the relationship between the clinical outcome of chronic HBV infection and the host's cellular immunity.[Methods]:46 volunteers from Peking Union Medical College Hospital and the Third Qinhuangdao Hospital were divided into 4 groups according to their clinic outcomes:13 patients with chronic hepatitis B;10 chronic HBV carders,10 inactive HBsAg carriers;and 13 volunteers with resolved subclinical HBV infection.Flow cytometry was used to detect CCR7/CD27 CD8+ T lymphocytes subsets.It was also used to detect frequencies of both non-specific IFN-γ+CD8+ T cells and HBcAg-specific IFN-γ+CD8+ T cells.HBcAg peptides library including 3 peptides pools was designed as stimulator to test HBcAg-specific CD8+T cells.The stimulator for non-specific CD8+ T cell reactions was PMA+Ionomycin.[Results]:1) Frequency of peripharal blood CD8+CCR7-CD27- T cells in chronic hepatitis B patients was 57.1%±20.5%,which was significantly higher than those of chronic HBV carriers,inactive HBsAg carders and recovered HBV patients.While in contrast,frequency of CD8+CCR7+CD27+T cells in chronic hepatitis B patients was 23.1%±14.6%,much lower than those of the other 3 groups.2) Upon stimualtion by PMA+Ionomycin for 20 hours,frequencies of INF-γpositive CD8+ T cells in chronic hepatitis B patients,chronic HBV carders and inactive HBsAg carders were 12.405%(7.716%,17.320%),12.850%(7.042%,23.007%) and 20.333%(15.345%,29.698%),respectively.Frequencies of INF-γpositive CD8+CCR7-CD27+ T cells and INF-γpositive CD8+CCR7-CD27-T cells,were 11.042% (5.219%,14.750%) and 44.409%(25.823%,47.427%),respectively,both higher than those of chronic hepatitis B patients and chronic HBV carriers.3) Upon stimulation by HBcAg AAs 61-130 peptide pool,frequencies of INF-γpositive specific CD8+ T cells in chronic hepatitis B patients,chronic HBV carriers,inactive HBsAg carriers and recovered HBV patients were 0.042%(0,0.076%),0(0,0.032%), 0.068%(0.029%,0.151%) and 0.005%(0,0.010%),respectively.Responses to this very peptide pool in inactive HBsAg carriers were significantly stronger than those of chronic HBV carriers and recovered HBV patients,and stronger than those of chronic hepatitis B patients.Upon stimulation by HBcAg AAs 61-130 peptide pool,frequency of INF-γpositive CD8+CCR7-CD27+ T cells in inactive HBsAg carriers was 0.103%(0.063%,0.234%), significantly higher than those of chronic hepatitis B patients,chronic HBV carriers and recovered HBV patients(P＜0.009).While in responses to the same peptide pool,frequencies of INF-γpositive CD8+CCR7-CD27- T cells in inactive HBsAg carriers and chronic hepatitis B patients were 0.034%(0.008%,0.131%) and 0.033%(0%,0.11%) respectively, both significantly higher than that of recovered HBV patients.(P＜0.009).[Conclusions]:1) CD8+ T lymphocyte dysfuntion exists in chronic HBV infection.Compared with chronic hepatitis B patients and chronic HBV carriers,inactive HBsAg carriers have stronger non-specific CD8+ T cellular immunity.2) HBcAg-specific CD8+T cell responses in inactive HBsAg carriers are stronger than those in chronic hepatitis B patients,chronic HBV carriers and recovered HBV patients. HBcAg-specific CD8+T cells are playing important roles in clearance of HBV.3) The key epitopes in HBcAg which can activate host's immuno-response to clear HBV are probably covered by amino acid sequencies 1-130.4) CD8+CCR7-CD27+ T lymphocytes probably play important roles in the immune pathogenesis of chronic HBV infection.