The Expression Of Chemokine Receptors CCR5,CXCR3,CXCR6 And CXCR7 On T Lymphocytes In Liver And Peripheral Blood With Primary Biliary Cirrhosis And Its Significance

ObjectivesTo provide a comprehensive comparison of expression of chemokine receptors CCR5, CXCR3,CXCR6 and CXCR7 on T lymphocytes in liver and peripheral blood with Primary biliary cirrhosis(PBC),and its correlation with histopathological inflammation activity of liver,in order to facilitate recognition and preliminary study of pathogenesis of PBC on the basis of chemokines and their receptors.Methodsliver tissue biopsy specimens and blood samples of 11 cases of diagnosed patients with PBC were collected from Department of Hepatopancreatobiliary,the Second Hospital Affiliated of Kunming Medical College in February 2008～December 2008 hospitalization.And we applied Beckman Coulter Epics XL flow cytometry to make detection of CCR5,CXCR3,CXCR6 and CXCR7 expression on lymphocytes in liver and peripheral blood,and analyzed the results.Results1.The general information in eleven patients with PBC:the mean age was 43.3±14.6 years old,the ratio of female to male was 7:4 among the 11 patients.There were seven cases of PBCⅢ-ⅣandⅣperiod,while the rest were under or to the stage of PBCⅡ.2.The main liver tissue-infiltrating lymphocytes were CD8+ and CD4+ T lyrnphocytes.CD4+ T lymphocytes were predominant in peripheral blood.CD8 + T lymphocytes were higher in liver tissue than in peripheral blood,while B lymphocytes in liver tissue and peripheral blood showed no significant difference (P＞0.05).CD4+ T lymphocytes were higher in peripheral blood than in liver tissue(P＜0.05).No statistical difference was showed on the above-mentioned liver-infiltrating lymphocyte subsets between groups of different degrees of liver histological inflammation(P＞0.05).3.CCR5,CXCR3 and CXCR6 were all expressed higher in liver tissue than in peripheral blood(P＜0.001),while the expression of CXCR7 in liver tissue was in significantly lower level than that of CCR5,CXCR3 and CXCR6,even though its expression level was still higher in the liver tissue than in the peripheral blood (P＜0.05).4.CXCR6 of the severe liver disease group expressed slightly higher than that of the lesion group,while CCR5,CXCR3 and CXCR7 expression levels showed no statistical difference(P＞0.05).5.Cytokines IL-2,IL-4,IL-5,IL-10,IFN-γand TNF-αwere significantly increased, but no statistical difference was showed on their expressions in liver tissues compared with those in the blood(P＞0.05).Conclusions1.PBC and immune dysfunction are closely related,and CD8+T cell,CD4+T cell-mediated immune responses play a more important role in autoimmune response.It may be responsible for an important mechanism for injury in its own target organ—bile duct epithelial cells.2.CCR5,CXCR3 and CXCR6 are liver trafficking chemokine receptors which mediate homing T lymphocytes to liver,and may play an important role in the regulation of immunopathologic reaction of PBC.3.CXCR6 leading lymphocytic infiltration to liver may play a more important role in mechanisms of liver injury of PBC. 4.CXCR7 may have a minor role in homing T lymphoeytes to liver.5.Cytokines,especially IL-2 and IFN-γmay be involved in the formation of PBC pathology.