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Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients

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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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Acknowledgments

This work was supported by the Key Research Projects of National 12th Five-year Plan for the Prevention and Treatment of Major Infectious Diseases 2012ZX10001003-003, 2012ZX10001003-001, Guangdong Innovative Research Team Program 2009010058, National Natural Science Foundation of China 81072397, Natural Science Foundation of Guangdong S2011010005587, S2011020006072, the Fundamental Research Funds for the Central Universities (to J.Z.). We are grateful to the volunteers who participated in this study.

Conflict of interest

The authors declare no conflict of intest exists.

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Authors and Affiliations

  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

    Weiping Cai, Pengle Guo, Fengyu Hu, Min Xu & Xiaoping Tang

  2. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    Aiping Qin, Dehong Yan, Qiong Yang & Jie Zhou

  3. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen Univeristy, Guangzhou, China

    Yongshui Fu

  4. Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, China, 510080

    Jie Zhou

  5. Guangzhou Blood Center, Guangzhou, China

    Yongshui Fu

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  1. Weiping Cai
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  2. Aiping Qin
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  3. Pengle Guo
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  7. Min Xu
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  9. Jie Zhou
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  10. Xiaoping Tang
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Corresponding authors

Correspondence to Jie Zhou or Xiaoping Tang.

Additional information

Weiping Cai and Aiping Qin contributed equally to this work.

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Cai, W., Qin, A., Guo, P. et al. Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients. J Clin Immunol 33, 798–808 (2013). https://doi.org/10.1007/s10875-012-9861-2

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  • DOI: https://doi.org/10.1007/s10875-012-9861-2

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