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目的定量检测原发性胆汁性肝硬化(PBC)患者体内抗原特异性T淋巴细胞含量,探讨其在PBC发病机制中的作用。方法采用四聚体技术检测15例HLA-A0201阳性(A2+)PBC患者外周血单个核细胞(PBMC)经抗原肽诱导生长的细胞毒性T淋巴细胞(CTL)中PDC-E2159~167aa与PDC-E2165~174aa特异性CD8+T细胞频率,以A0201阴性(A2-)PBC患者与A2+的其他慢性肝病和健康自愿者为对照组。结果在A2+PBC患者PDC-E2159~167aa与PDC-E2165~174aa诱导的CTL中可检测到其相应的四聚体/CD8+细胞,平均频率分别为0.42%±0.24%(0.17%~1.08%)、0.27%±0.17%(0.05%~0.56%),各对照组的四聚体阳性细胞频率均低于0.1%,差异非常显著(P<0.001);A2+PBC组中PDC-E2159~167aa特异性的CTL频率与PDC-E2165~174aa特异性的CTL无显著性差异(P>0.05)。处于临床Ⅰ、Ⅱ期的A2+PBC患者中CD8+特异性CTL频率均较Ⅲ期的要高(P<0.05)。PDC-E2159~167aa特异性CTL与PDC-E2165~174aa特异性CTL频率在抗-PDC阳性PBC组和抗-PDC阴性组之间均无显著性差异(P>0.05)。结论HLA-A0201限制性的PDC-E2159~167aa和PDC-E2165~174aa特异性CD8+CTL在PBC疾病进展中起重要作用,抗线粒体抗体阴性或抗-PDC阴性PBC患者与阳性患者可能有着相似的T细胞介导的免疫发病机制。
Objective To quantitatively detect the level of antigen-specific T lymphocytes in patients with primary biliary cirrhosis (PBC) and to explore its role in the pathogenesis of PBC. Methods Tetramer technique was used to detect the expression of PDC-E2159 ~ 167aa and PDC-E2165 in CTL induced by antigen peptides in peripheral blood mononuclear cells (PBMCs) from 15 HLA-A0201 positive (A2 +) PBC patients. ~ 174aa specific CD8 + T cell frequency in A0201 negative (A2-) PBC patients with A2 + other chronic liver disease and healthy volunteers as the control group. Results The corresponding tetramer / CD8 + cells were detected in the CTL induced by PDC-E2159 ~ 167aa and PDC-E2165 ~ 174aa in A2 + PBC patients with the average frequencies of 0.42% ± 0.24% (0.17% ~ 1.08% , 0.27% ± 0.17% (0.05% -0.56%). The frequencies of tetramer positive cells in each control group were all less than 0.1% (P <0.001). The frequencies of PDC-E2159 ~ 167aa in A2 + PBC group There was no significant difference in sex CTL frequency and PDC-E2165 ~ 174aa specific CTL (P> 0.05). The frequency of CD8 + specific CTLs in stage I and II A2 + PBC patients was higher than that in stage III (P <0.05). There was no significant difference between PDC-E2159 ~ 167aa specific CTL and PDC-E2165 ~ 174aa specific CTL frequency in anti-DCC positive PBC group and anti-DCC negative group (P> 0.05). Conclusions HLA-A0201-restricted PDC-E2159-167aa and PDC-E2165-174aa-specific CD8 + CTLs play an important role in the progression of PBC disease. Patients with anti-mitochondrial antibody or anti-PDC negative PBC may have similar T cell-mediated immune pathogenesis.