Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2007; 13(7): 1060-1066
Published online Feb 21, 2007. doi: 10.3748/wjg.v13.i7.1060
Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice
Xiao-Jun Ma, De-Ying Tian, Dong Xu, Dao-Feng Yang, Hui-Fen Zhu, Zhi-Hui Liang, Zheng-Gang Zhang
Xiao-Jun Ma, De-Ying Tian, Dong Xu, Dao-Feng Yang, Zheng-Gang Zhang, Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Hui-Fen Zhu, Zhi-Hui Liang, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 30471533
Correspondence to: Dr. De-Ying Tian, Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095,Wuhan 430030, Hubei Province, China. langz2004@126.com
Telephone: +86-27-69807982 Fax: +86-27-83613408
Received: November 12, 2006
Revised: December 5, 2006
Accepted: December 25, 2006
Published online: February 21, 2007
Abstract

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 × 106) 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-γ secreted by splenocytes was higher (266.575 ± 51.323 vs 135.223 ± 32.563, P < 0.01) , and IL-4 level was lower (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.

Keywords: Uric acid, Dendritic cells, Hepatitis B virus surface antigen, Cytotoxic T lymphocytes, Mouse