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

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Abstract
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 Bcl‐2‐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 of T 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).