1999 Fiscal Year Final Research Report Summary
Abnormalities of immune regulation in autoimmune hepatitis and their modulation by TGF-β
| Project/Area Number |
09670552
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
SAKAGUCHI Kohsaku Okayama University, Medical School Hospital, Assistant, 医学部・附属病院, 助手 (90235143)
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| Project Period (FY) |
1997 – 1999
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| Keywords | autoimmune hepatitis / Peripheral lymphocytes / CD95 / TGF-β / TGF-β receptor |
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| Research Abstract |
Autoimmune hepatitis (AIH) is a chronic active hepatitis, in which abnormalities of immune regulation have been suspected to play a role in the induction of autoimmunity. Recently, the peripheral immune system have been appeared to possess mechanisms to control an autoimmune aberration by the elimination, by apoptosis, of autoreactive or unnecessary lymphocytes activate by antigenic stimuli. The transmembrane protein CD95 (Fas/APO-1) plays a role in the apoptotic death of antigen-activated lymphocytes. In this study, we examined the levels and distributional expressions of CD95 and Bcl-2 on freshly isolated lymphocytes from patients with AIH by flow cytometric analysis. The surface expression of CD95 was significantly high in both the CD4ィイD1+ィエD1 T and CD8ィイD1+ィエD1 T cell subsets derived from the patients with AIH, compared with expression in patients with chronic hepatitis C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of native CD45ROィイD1-ィエD1 to primed CD45ROィイD1+ィエD1 T cells. These results indicate that the expanded CD95ィイD1+ィエD1 CD45ROィイD1+ィエD1 primed T cell most likely reflect a continuous activation of T lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. On the other hands, transforming growth factor-β (TGF-β) has been shown to exert several immunosuppressive effects. We investigated the level of serum TGF-β and the expression of TGF-β receptor II (TβRII) on peripheral blood monocular cells, in order to evaluate the role of TGF-β in the abnormalities of immune regulation. The level of serum TGF-β was significantly greater in the patients with AIH, while the expression of TβRII on PBMC was decreased. The decreased TβRII expression on PBMC suggests that a reduction in TβRII expression on PBMC results in attenuation of immunosuppression signals from TGF-β.
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