Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients.
OBJECTIVE
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.


CONCLUSIONS
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.
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
W
Cai
Aiping
A
Qin
Pengle
P
Guo
Dehong
D
Yan
Fengyu
F
Hu
Qiong
Q
Yang
Min
M
Xu
Yongshui
Y
Fu
Jie
J
Zhou
Xiaoping
X
Tang
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001119:Arginase / Q000378:metabolism; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016898:Interferon-alpha / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects; D012254:Ribavirin / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; C574619:ARG1 protein, human; D001119:Arginase