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01 奈良県立医科大学 >
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01121 Journal of Nara Medical Association >
Vol.49 No.6 >
このアイテムの引用には次の識別子を使用してください:
http://hdl.handle.net/10564/479
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タイトル: | ウルソデオキシコール酸のT cell-rnediated target apoptosisに及ぼす影響 |
その他のタイトル: | EFFECTS OF URSODEOXYCHOLIC ACID ON T CELL-MEDIATED TARGET APOPTOSIS |
著者: | 川本, 博 |
キーワード: | ursodeoxycholic acid apoptosis T cell-mediated cytotoxicity Fas Fas-legand |
発行日: | 1998年12月31日 |
出版者: | 奈良医学会 |
引用: | Journal of Nara Medical Association Vol.49 No.6 p.442-452 |
抄録: | 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 |
出現コレクション: | Vol.49 No.6
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