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Study Of CXCR3on CD8+T Cells In Primary Biliary Cirrhosis

Posted on:2015-11-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:1224330431972886Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objects To exploit the role of CXCR3on lymphocytes, especially CD8+T cells in primary biliary cirrhosis (PBC) by detecting serum levels of CXCR3ligands, CXCR3expression on cell membrane and CXCR3mRNA in nucleus. Therefore, to achieve more comprehensive understanding of the mechanism of CXCR3in PBC.Methods Part1serum chemokine detection by cytometric bead array (CBA).31PBC patients,21of which have elevated ALP,7Chronic Hepatitis B (CHB) patients as disease control and13age-matched healthy controls are enrolled. Serum concentrations of MIG (CXCL9), IP-10(CXCL10), I-TAC (CXCL11) are detected using CBA at one time. Part2The method of flow cytometry (FCM) immunofluorescence is used to detect CD8+ratio of all lymphocytes. Expression of CXCR3on cell membrane of lymphocytes and CD8+cells are determined by direct immune-staining.12PBC patients,10of which have elevated ALP,7disease controls and13age-matched healthy controls are enrolled. Part3Real-time polymerase chain reaction is used to detect mRNA of the gene CXCR3in peripheral CD8+cells using the gene GAPDH as endogenous control.9PBC patients,8of which have elevated ALP,7disease controls and9age-matched healthy controls are enrolled.Results Part1All3ligands of CXCR3are significantly elevated in PBC patients than controls. PMIG-DC=0.002, PMIG-HC<0.001, PIP-10-DC=0.011, PIP-10-HC<0.001, PI-IAC-DC=0.006, PI-TAC-HC<0.001.There are no significant differences between the results of2control groups. However ALP elevated PBC patients shows no difference than those with normal ALP levels. Part2CD8+ratios of all3groups are unanimous. Lymphocytes of PBC patients show significant elevation of CXCR3expression than controls. P values are0.006and0.024. Results of CD8+cells are consistent with lymphocytes. P values of PBC group versus2control groups are0.007and0,039respectively. Part3The mRNA expression of CXCR3gene of all3groups show no variance. Conclusions Serum concentrations of MIG, IP-10and I-TAC are significantly elevated in PBC patients than controls, regardless of ALP level. PBC patients also show higher expression of CXCR3on lymphocytes and CD8+cells, indicating that CXCR3may play a role in the recruitment of CD8+T cells in PBC. However, the even mRNA expression of PBC patients and controls suggests the existence of post-trascription regulation mechanism.
Keywords/Search Tags:Primary Biliary Cirrhosis, PBC, CXCR3, CD8+T cell
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