Autoreactive CD4+ LKM-specific and anticlonotypic T-cell responses in LKM-1 antibody-positive autoimmune hepatitis
In: Hepatology (Baltimore, Md.), Jg. 24 (1996), Heft 6, S. 1416-1421
Online
academicJournal
- print, 40 ref
Zugriff:
Peripheral blood mononuclear cells (PBMC) of patients with autoimmune hepatitis (AIH) and controls were studied for their proliferative response to six overlapping synthetic peptides covering the 33-amino acid immunodominant region of cytochrome P450IID6, the main target antigen of LKM-1 antibody-positive type II AIH. PBMC from 8 of 8 type II AIH patients (100%), 6 of 12 LKM-1 antibody-negative type I AIH patients (50%), but only 4 of 31 patients with chronic hepatitis C (12.9%) reacted with a 23-amino acid LKM peptide and mainly with a shorter 18-amino acid LKM peptide. Follow-up showed that LKM-specific T-cell responses decreased after immunosuppression had started. Fine specificity, HLA restriction, and cytokine release of LKM-specific T cells were analyzed with 16 CD4+ peptide-specific T-cell lines and 21 CD4+ T-cell clones isolated and expanded from blood and liver tissue of six AIH patients. Activated LKM-specific T cells released interferon gamma (IFN-γ) but no or little interleukin-4. In three AIH patients, PBMC showed specific recognition of autologous LKM-specific T cells, suggesting the presence of a regulatory T-cell network. These T cells also showed the CD4+ phenotype and secreted large amounts of IFN-γ. Furthermore, it was assessed that the regulatory T-cell response is clonotypic. To conclude, we describe a major T-cell epitope in AIH that was recognized by Th1 helper cells isolated from blood and liver tissue. This autoreactive T-cell response correlated widely with disease activity and LKM-1 antibody status and seemed to be regulated by anticlonotypic T cells.
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Autoreactive CD4+ LKM-specific and anticlonotypic T-cell responses in LKM-1 antibody-positive autoimmune hepatitis
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Autor/in / Beteiligte Person: | LÖHR, H. F ; SCHLAAK, J. F ; LOHSE, A. W ; BÖCHER, W. O ; ARENZ, M ; GERKEN, G ; MEYER ZUM BÜSCHENFELDE, K.-H |
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Zeitschrift: | Hepatology (Baltimore, Md.), Jg. 24 (1996), Heft 6, S. 1416-1421 |
Veröffentlichung: | Hoboken, NJ: Wiley, 1996 |
Medientyp: | academicJournal |
Umfang: | print, 40 ref |
ISSN: | 0270-9139 (print) |
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