Liu Hai-ying, Zhang Jian, Deng An-mei, Geng Hong-lian, Zhou Lin, Zhu Ye, Xu De-xing, Zhong Ren-qian
Clinical Laboratory, General Hospital of Guangzhou, Guangzhou 510010, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2006 Jan;22(1):78-81.
To quantitate antigen specific T lymphocytes in peripheral blood from patients with primary biliary cirrhosis(PBC) and study the role of antigen specific T lymphocytes in the development of PBC.
Using tetramers and CD8 monoclonal antibody staining, PDC-E2 159-167aa and PDC-E2 165-174aa specific CD8(+) T lymphocytes were determined respectively in the peptide-induced cytotoxic T cell lines prepared from peripheral blood mononuclear cells(PBMC) of 15 PBC patients. The frequencies of these two kinds of antigen specific T lymphocytes in HLA-A*0201 positive (A2(+)) PBC were compared with those in A2(-) PBC patients, patients with other A2(+) chronic liver diseases and healthy controls.
PDC-E2 159-167aa/HLA-A0201 and PDC-E2 165-174aa/HLA-A0201 tetramer positive CD8(+) T lymphocytes were detected in all of A2(+) PBC patients with average percentages of 0.42%+/-0.24% (0.17%-1.08%) and 0.27%+/-0.17% (0.05%-0.56%), respectively. The frequencies of the two kinds of antigen specific CD8(+) T lymphocytes from peripheral blood were significantly higher in earlier stages I and II of PBC as compared with stage III (P<0.001), while no difference was found between PDC-E2 159-167aa and PDC-E2 165-174aa specific CD8(+) T lymphocytes at the same stages. In addition, there existed no statistical difference between frequencies of antigen specific T lymphocytes in AMA or anti-PDC positive and negative PBC patients (P>0.05).
This study suggests that HLA-A*0201 restricted PDC-E2 165-174aa and PDC-E2 159-167aa specific CTL play important roles in the development of PBC, and there might be a similar mechanism of T cell-mediated damage between AMA or anti-PDC positive and negative PBC patients.
定量分析原发性胆汁性肝硬化(PBC)患者外周血中抗原特异性T淋巴细胞,并研究抗原特异性T淋巴细胞在PBC发病中的作用。
采用四聚体和CD8单克隆抗体染色,分别检测15例PBC患者外周血单个核细胞(PBMC)制备的肽诱导细胞毒性T细胞系中PDC-E2 159-167aa和PDC-E2 165-174aa特异性CD8(+) T淋巴细胞。比较HLA-A*0201阳性(A2(+))PBC患者与A2(-) PBC患者、其他A2(+)慢性肝病患者及健康对照者外周血中这两种抗原特异性T淋巴细胞的频率。
在所有A2(+) PBC患者中均检测到PDC-E2 159-167aa/HLA-A0201和PDC-E2 165-174aa/HLA-A0201四聚体阳性CD8(+) T淋巴细胞,平均百分比分别为0.42%±0.24%(0.17%-1.08%)和0.27%±0.17%(0.05%-0.56%)。与III期相比,PBC I期和II期外周血中这两种抗原特异性CD8(+) T淋巴细胞的频率显著更高(P<0.001),而同一阶段PDC-E2 159-167aa和PDC-E2 165-174aa特异性CD8(+) T淋巴细胞之间无差异。此外,AMA或抗PDC阳性和阴性PBC患者的抗原特异性T淋巴细胞频率之间无统计学差异(P>0.05)。
本研究提示,HLA-A*0201限制性PDC-E2 165-174aa和PDC-E2 159-167aa特异性CTL在PBC发病中起重要作用,AMA或抗PDC阳性和阴性PBC患者之间可能存在相似的T细胞介导损伤机制。