Increase in CD95 (Fas/APO-1)-positive CD4⁺ and CD8⁺ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

Background: The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). Methods: The CD95 and Bcl-2 expressions within CD4⁺ T, CD8⁺ T, and CD19⁺ B cell subsets were analysed by two-colour flow cytometry. Results: The surface expression of CD95 was significantly high in both the CD4⁺ T and CD8⁺ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO^- to primed CD45RO⁺ CD4⁺T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl2- positive cells in the CD4⁺T cell, CD8⁺T cell and CD19⁺ B cell subsets among the patient groups and normal subjects. Conclusions: These results indicate that an increase in CD4⁺T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95⁺ CD45RO⁺ primed T cells most likely reflect a continuous antigen-specific or non- specific activation oft lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI). (C) 2000 Blackwell Science Asia Pty Ltd.