Autoreactive helper T cells specific for cytokeratin 19 in patients with autoimmune hepatitis

Hepatol Res. 2003 Apr;25(4):415-422. doi: 10.1016/s1386-6346(02)00314-5.

Abstract

Recently we have demonstrated the existence of anti-cytokeratin 19 (CK19) antibodies in sera of patients with autoimmune hepatitis (AIH). In the present study, we examined the existence of T lymphocytes specific for CK19 in patients with AIH. The frequency of responders having CK19-specific T lymphocytes was significantly higher in AIH patients than in chronic hepatitis C (CH-C) patients and normal subjects. Furthermore, the stimulation index of proliferative responses of peripheral blood mononuclear cells (PBMCs) was significantly higher in AIH patients than in CH-C patients and normal subjects. The phenotype of proliferating PBMCs specific for CK19 was shown to be predominantly CD4(+) T lymphocytes and these CD4(+) T lymphocytes had a Th1 subtype. The present findings demonstrate that there is some population of CD4(+) T lymphocytes with a Th1 subtype specific for CK19 in peripheral blood of patients with AIH. The Th1-predominat pattern of cytokines may induce cytotoxic T lymphocytes (CTLs) specific for the antigenic peptides derived from the autoantigen, including CK19. In addition, these CTLs may attack the hepatocytes and this may be one of the important etiologies of AIH.