| Chemokine Receptor Expression of Hepatitis B Virus-Specific CD8+ Lymphocyte
in Chronic B Viral Infection |
| Chun Kyon Lee, M.D.1, Jeong Hun Suh, M.D.1, Young Suk Cho, M.D.1, Kwang-Hyub Han, M.D.2,
Jae Bock Chung, M.D.1,2, Chae Yoon Chon, M.D.2 and Young Myoung Moon, M.D.2 |
| Department of Internal Medicine, National health insurance corporation Ilsan Hospital1, Koyang, Korea,
Department of Internal Medicine, Yonsei University College of Medicine2, Seoul, Korea |
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| ABSTRACT |
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Background/Aims
The protective role of HBV-specific CD8+ cells is dependent on their ability to efficiently migrate to the infected liver, where they may exert an effector function. The migratory behavior of CD8+ cells is influenced by their expression of different chemokine receptors. This study was intended to analyse the pattern of chemokine receptor expression of HBV specific CD 8+ cells in chronic B viral infection. Methods: We analysed the CCR5 and CCR3 profile of HBV-specific CD8+ cells isolated from the blood and liver of patients with different patterns of HBV infection. Purified T cells were stained directly ex vivo, or after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry. Results: In patients with chronic hepatitis B characterised by low levels of virus (serum HBV DNA <0.5pg/mL) and minimal liver inflammation, analysis of circulating and intrahepatic CD8+ cells demonstrated that liver infiltrating Tc18-27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8+ cells), in contrast to cells of the same specificity within the circulating compartment (up to 35% of HBV-specific CD8+ cells). Furthermore, CCR3 was expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent from circulating cells. Following HBV-specific stimulation in vitro the CCR5 expression of circulating Tc18-27-specific cells was up-regulated, to levels found in liver infiltrating cells, whereas CCR3 expression was unchanged. Conclusions: The chemokine receptor profile of HBV-specific CD8+ cells is influenced by the anatomical site of these cells, and the clinical pattern of disease. The ability of circulating HBV-specific CD8+ cells of patients with low replicating virus to upregulate CCR5 suggests that these cells may respond to increases in virus replication by efficiently migrating into the infected liver. (Korean J Hepatol 2002;8:363-370) |
| KeyWords:
Hepatitis/Viral/Chronic hepatitis B, HBV-specific CD8+ lymphocyte, Chemokine receptor |
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