Correlation between clinical stages of HBV chronic infection and co-expression of CD244 and PD-1 in HBV-specific CTLs |
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Authors: | WANG Jiao DENG Hong XIE Dong-ying ZHU Jian-yun HU Zhao-xia MEI Ming-zhu GAO Zhi-liang |
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Institution: | 1.Department of Infectious Diseases, ;2.Vaccine Research Center, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China |
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Abstract: | AIM: To investigate the co-expression of cluster of differentiation 244 (CD244) and programmed death 1 protein (PD-1) on hepatitis B virus (HBV) antigen-specific cytotoxic T-lymphocytes (CTLs) in chronic hepatitis B (CHB) patients and its correlation with the clinical stages of HBV chronic infection. METHODS: Eighty-one CHB subjects with human leukocyte antigen-A2 (HLA-A2) positive, including 20 cases of acute-on-chronic liver failure (ACLF), 20 cases of severe chronic hepatitis B (s-CHB), 34 cases of mild and moderate chronic hepatitis B (m-CHB) and 7 cases of immune tolerant stage (IT) of chronic hepatitis B as well as 14 healthy controls (HC), were enrolled in this study. The co-expression of CD244 and PD-1 was analyzed in virus-specific CD8+ T-cells derived from peripheral blood using major histocompatibility complex class I (MHC-I) pentamers targeting immunodominant epitopes of HBV core antigen (18-27). RESULTS: In the patients with chronic HBV infection, virus-specific CD8+T-cells with co-expression of CD244 and PD-1 were at increased levels than those in total CD8+ T-cells (67.48%±17.16% vs 14.01%±7.97%, P<0.01) in the peripheral blood. Among different clinical stages, increased level of CD244 expression coincided with increased expression of PD-1 in m-CHB compared with IT of CHB (73.08%±8.63% vs 53.11%±18.05%, P<0.05), which was followed by decreased co-expression level in ACLF (63.11%±13.87% vs 72.05%±16.86%, P<0.05) and restoration of the ability to secrete IFN-γ (30.95%±20.29% vs 13.63%±10.46%, P<0.05). CONCLUSION: CD244 and PD-1 are highly co-expressed in HBV-specific CTLs in the patients with s-CHB and m-CHB, and are decreased in ACLF following the restoration of IFN-γ secretion. The severity of CHB may be correlated with CD244 and PD-1 co-expression in HBV-specific CTLs. |
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Keywords: | Hepatitis B chronic T-lymphocytes cytotoxic Programmed death 1 protein CD244 |
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