373 REDUCED HEPATITIS B VIRUS SURFACE ANTIGEN EXPRESSION IN OCCULT HEPATITIS B INFECTION: ALTERATION OF A POST-TRANSCRIPTIONAL REGULATORY MECHANISM?

Abstract

HBV infected patients (19 HBeAg neg., 1 HBeAg pos.) and compared it to Influenza (Flu)-, CMVand HCV-specific CD8+ T cells. In addition, the functional relevance of inhibitory receptor blockade (PD-1, 2B4, Tim-3, CTLA-4, BTLA) was tested in in vitro assays. Results: HBV-specific CD8+ T cells expressed higher amounts of PD-1 and 2B4 compared to CD160, KLRG1 and Tim-3. The PD-1+2B4+ HBV-specific CD8+ T cells were enriched in the liver compared to the peripheral blood. The expression pattern of inhibitory receptors clearly differed between HBV-specific (high PD-1 and 2B4 expression) versus FLU(high Tim 3 expression) or CMV-specific CD8+ T cells (high 2B4 and KLRG1 expression). In contrast, a similar high expression of PD-1 and 2B4 was observed on HCV-specific CD8+ T cells, suggesting a common hierarchy of inhibitory receptor expression between CD8+ T cells specific for hepatitis B and C virus. However, coexpression analysis revealed a lower coexpression of inhibitory receptors on HBV-specific CD8+ T cells compared to exhausted HCV-specific CD8+ T cells. The subsequent blockade of inhibitory receptors resulted in individual functional response patterns regarding in vitro proliferation or antiviral efficacy. Conclusions: These results suggest a clear hierarchy of inhibitory receptor expression on HBV-specific CD8+ T cells that is dominated by PD-1 and 2B4. Compared to exhausted HCV-specific CD8+ T cells, HBV-specific CD8+ T cells appear less severely exhausted. These findings have implications for therapeutic interventions targeting exhausted T cells during chronic HBV infection.