Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

AIM： To study the induction of T cellular immune responses in BALB/c mice immunized with uric acid and dendritic cells （DCs） pulsed with hepatitis B virus surface antigen （HBsAg）. METHODS： DCs were generated from bone-marrow cells of BABL/c mice, and then pulsed or unpulsed with HBsAg protein （HBsAg-pulsed-DCs or unpulsed-DCs） in vitro. BABL/c mice were immunized with HBsAg-pulsed- DCs （1 × 10^6） and uric acid, injected through the tail vein of each mouse. The mice in control groups were immunized with HBsAg-pulsed-DCs alone, unpulsed- DCs alone or 200 μg uric acid alone or PBS alone. The immunization was repeated 7 d later. Cytotoxic T lymphocytes （CTLs） in vivo were determined by the CFSE labeled spleen lysis assay. Spleen cells or spleen T cells were isolated, and re-stimulated in vitro with HBsAg for 120 h or 72 h. Production of IFN-γ, and IL-4 secreted by spleen cells were determined by ELISA method; proliferation of spleen T cells were detected by flow cytometry. RESULTS： The cytotoxicities of HBsAg-specific-CTLs, generated after immunization of HBsAg-pulsed-DCs and uric acid, were 68.63% ±11.32% and significantly stronger than that in the control groups （P 〈 0.01）. Compared with control groups, in mice treated with uric acid and HBsAg-pulsed-DCs, the spleen T cell proliferation to HBsAg re-stimulation was stronger （1.34 ± 0.093 vs 1.081±0.028, P 〈 0.01）, the level of IFN-t, secreted by splenocytes was higher （266.575 ± 51.323 vs 135.223 ±32.563, P 〈 0.01） , and IL-4 level wasower （22.385 ± 2.252 vs 40.598 ± 4.218, P 〈 0.01）. CONCLUSION： Uric acid can strongly enhance T cell immune responses induced by HBsAg-pulsed-DCs vaccine. Uric acid may serve as an effective adjuvant of DC vaccine against HBV infection.