Marked Decreases of Foxp3 and CTLA-4 Are Associated with Strong Antiviral Effects of Tenofovir in Patients with Chronic Hepatitis B = Marked Decreases of Foxp3 and CTLA-4 Are Associated with Strong Antiviral Effects of Tenofovir in Patients with Chronic Hepatitis B

다국어 초록 (Multilingual Abstract)

Aims: Immune regulatory molecules such as forkhead box P3 (Foxp3) on CD4+ T cell and cytotoxic T lymphocyte-associated antigen 4 CTLA-4) on CD8+ T cell are associated with antiviral effector T cell dysfunction, which influences on T cell exhaustion and persistent viral infection in patients with chronic hepatitis B. These Foxp3 and CTLA-4 are up-regulated in chronic hepatitis B. During antiviral therapy with tenofovir, the expressions of Foxp3 and CTLA-4 could be changed. We investigated the relationship between antiviral effects of tenofovir and the expression of Foxp3 and CTLA-4 during tenofovir treatment in chronic hepatitis B. Methods: Eight patients with chronic hepatitis B under tenofovir treatment were enrolled for detection of Foxp3 on CD4+ T cell and CTLA-4 on CD8+ T cell. Peripheral blood mononuclear cells were isolated from these subjects before tenofovir treatment (T0), 3 month (T3) and 6 month (T6) during tenofovir treatment. For antiviral effect analysis, serum HBV DNA levels were checked at same time. The expressions of Foxp3 and CTLA-4 on T cells were monitored by flow cytometry. Results: Three patients (3 of 8) showed marked decreases of Foxp3 and CTLA-4 during tenofovir therapy (group 1). Five patients (5 of 8) showed minimal changes of Foxp3 or CTLA-4 during tenofovir therapy (group 2). Group 1 showed complete virologic response within 6 month therapy regardless of baseline HBV DNA level but, group 2 showed complete virologic response within 6 month therapy only in patients with low baseline HBV DNA level (< 7log HBV DNA). Conclusions: Among the patients with chronic hepatitis B, the patients who showed marked decrease of Foxp3 and CTLA-4 during tenofovir therapy are associated with strong antiviral effects of tenofovir regardless of baseline HBV DNA level. This finding suggests that restoration of HBV-specific T cell strengthens the antiviral effects of tenofovir.