[Quantitation of antigen specific T lymphocytes in peripheral blood of patients with primary biliary cirrhosis using...

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-A*0201 and PDC-E2 165-174aa/HLA-A*0201 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.