Analysis of monocytic and granulocytic myeloid-derived suppressor cells subsets in patients with hepatitis C virus infection and their clinical significance

Abstract

Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14(+)HLA-DR(-/low) cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = -2.438, P = 0.015), while there was no statistical difference between the frequency of HLA-DR(-/low)CD33(+)CD11b(+)CD15(+) (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = -2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree.

Figure 1

Phenotypic analysis of MDSCs subsets in patients with HCV infection. PBMCs were obtained from patients (n = 68) and healthy control (n = 15). Fluorochrome-labeled antibodies targeting CD33, HLA-DR, CD15, CD14, and CD11b or the appropriate isotype controls were used to stained MDSCs. Then, MDSCs levels were evaluated by flow cytometry. (a) Flow cytometry analysis was performed with gates set on CD14⁺HLA-DR^−/low cells populations (M-MDSCs). (b) Flow cytometry analysis was performed with gates set on HLA-DR^−/lowCD33⁺CD11b⁺CD15⁺ cells populations (G-MDSCs).

Figure 2

Frequency of two MDSCs subpopulation in HCV patients and healthy control. (a) M-MDSCs from 68 HCV patients and 15 healthy donors. (b) G-MDSCs from 68 HCV patients and 15 healthy donors. (c) Frequency of M-MDSCs and G-MDSCs population in PMBC of HCV patients.

Figure 3

Frequency of two MDSCs subpopulation in CHC patients compared to hepatitis C cirrhosis patients. (a) M-MDSCs from 56 CHC patients and 12 hepatitis C cirrhosis patients. (b) G-MDSCs of 56 CHC patients and 12 hepatitis C cirrhosis patients.

Figure 4