Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients |
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Authors: | Weiping Cai Aiping Qin Pengle Guo Dehong Yan Fengyu Hu Qiong Yang Min Xu Yongshui Fu Jie Zhou Xiaoping Tang |
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Affiliation: | 1. Department of Infectious Diseases, the Affiliated Guangzhou No.8 People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Guangzhou No.8 People’s Hospitall, Guangzhou, China, 510080 2. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China 3. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen Univeristy, Guangzhou, China 5. Guangzhou Blood Center, Guangzhou, China 4. Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, China, 510080
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Abstract: | Purpose Myeloid-derived suppressor cells (MDSCs) are known to accumulate under some pathologic conditions and suppress immune system in a variety of ways. This study aims to evaluate the significance of MDSCs in chronic Hepatitis C (CHC) patients. Methods 14 CHC patients and healthy donors were enrolled and subject to antiviral therapy including Peg-INF-alpha and Ribavirin for 48 weeks. The peripheral blood mononuclear cells (PBMCs) were collected at different weeks post-therapy and MDSC frequency was analyzed by flow cytometry. The correlation between MDSCs level with CHC disease parameters was analyzed by Spearman’s rank test. The suppressive function of MDSCs from CHC patients and the underlying mechanism was further evaluated. Results A significant elevation of MDSCs was observed in the peripheral blood of treatment-naive CHC patients compared with healthy donors. The level of MDSCs in CHC patients correlated with plasma HCV-RNA (r?=?0.7164, p?=?0.0039), blood aminotransaminase (r?=?0.6116, p?=?0.021), and activated CD38+ T cells (CD4+: r?=?0.6649, p?=?0.0095; CD8+: r?=?0.6189, p?=?0.0189). Initiation of clinical therapy reduced MDSC levels as early as 4 weeks, while it rebounded at week 12 post-therapy in patients. CHC-derived MDSCs could suppress T cell function in an arginase-1-dependent manner, that was distinct from the HCV core protein-generated MDSCs as previously reported. Conclusion Our study reveals a significant correlation between MDSC levels with HCV disease progression, and their response to antiviral therapy. The arginase-1-dependent mechanism of MDSCs from CHC patients indicates that arginase-1 may be promising target for HCV immunotherapy. |
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