Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients.
J Clin Immunol
; 33(4): 798-808, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23354838
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite C Crônica
/
Células Mieloides
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article