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01121 Journal of Nara Medical Association >
Vol.49 No.6 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/479

Title: ウルソデオキシコール酸のT cell-rnediated target apoptosisに及ぼす影響
Authors: 川本, 博
Keywords: ursodeoxycholic acid
T cell-mediated cytotoxicity
Issue Date: 31-Dec-1998
Publisher: 奈良医学会
Citation: Journal of Nara Medical Association Vol.49 No.6 p.442-452
Abstract: The effectiveness of UDCA has been proven in the treatment of not only primary biliary cirrhosis but also chronic viral hepatitis, in which the apoptotic death of hepatocytes induced by cytotoxic T lymphocytes (CTLs) is suggested to be involved. To elucidate immunologically why UDCA is effective, we investigated the effects of UDCA on T cell-mediated apoptosis of target cells using a Fas-expressing murine B lymphoma line as targets/antigen presenting cells (APCs) and a murine CD4⁺ - T cell hybridoma line with a defined antigen specificity as effector T cells. The B lymphoma cell line, A20-HL, expresses MHC class Ⅱ antigen and is capable of acting as antigen presenting cells (APCs), and the T hybridoma line, 3 DO 54.8, is known to exhibit strong cytotoxicity against APCs after specific antigen stimulation with chicken ovalbumin (OVA). We used a synthetic OVA-oligopeptide, identical to the antigenic determinant for the OVA-specific T cells, as an antigen instead of the native OVA protein to exclude the influence of UDCA on APC function. The T cell-mediated cytotoxicity against APCs was investigated by conventional ⁵¹Cr release assay and DNA fragmentation assay. DNA fragmentation of APCs/target cells was observed after a 1-2h incubation period prior to the specific ⁵¹Cr release. FasL-mRNA in the effector cells was detected as early as 30 min after cocultiva- tion with APCs in the presence of OVA-peptide. UDCA suppressed the ⁵¹Cr release from target cells and also inhibited DNA fragmentation of target cells in a UDCA-dose depen- dent manner. In addition, mRNA synthesis of FasL in the effector T cells was suppressed by UDCA, although MHC class Ⅱ or Fas expression was not. Our study demonstrates that UDCA suppresses antigen-specific CD4⁺ - T cell-mediated target apoptosis by inhibiting the induction of FasL.
URI: http://hdl.handle.net/10564/479
ISSN: 13450069
Appears in Collections:Vol.49 No.6

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