[Chemokine receptor expression of hepatitis B virus-specific CD8+ lymphocyte in chronic B viral infection].
OBJECTIVE
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 <0.5 pg/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.
Lee
Chun Kyon
CK
Department of Internal Medicine, National health insurance corporation Ilsan Hospital, Koyang, Korea. cklee33@nhimc.or.kr
Suh
Jeong Hun
JH
Cho
Young Suk
YS
Han
Kwang-Hyub
KH
Chung
Jae Bock
JB
Chon
Chae Yoon
CY
Moon
Young Myoung
YM
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine