Fas-independent and nonapoptotic cytotoxicity mediated by a human CD4+ T-cell clone directed against an acute myelogenous leukemia-associated DEK-CAN fusion peptide

被引:38
作者
Ohminami, H
Yasukawa, M [1 ]
Kaneko, S
Yakushijin, Y
Abe, Y
Kasahara, Y
Ishida, Y
Fujita, S
机构
[1] Ehime Univ, Sch Med, Dept Internal Med 1, Shigenobu, Ehime 7910295, Japan
[2] Ehime Univ, Sch Med, Dept Pathol 1, Shigenobu, Ehime 7910295, Japan
[3] Ehime Univ, Sch Med, Dept Pediat, Shigenobu, Ehime 7910295, Japan
[4] Kanazawa Univ, Sch Med, Dept Pediat, Kanazawa, Ishikawa 920, Japan
关键词
D O I
10.1182/blood.V93.3.925.403k32_925_935
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The mechanism underlying the cytotoxicity mediated by a human CD4(+) cytotoxic T-lymphocyte (CTL) clone directed against a peptide derived from the acute myelogenous leukemia-associated fusion protein, DEK-CAN, was investigated. A DEK-CAN fusion peptide-specific CD4(+) Th0 CTL clone, designated HO-1, was established from the peripheral blood lymphocytes of a healthy individual. HO-1 exerted direct but not "innocent bystander" cytotoxicity within 2 hours. The cytotoxicity mediated by HO-1 was completely Ca2+-dependent. Because HO-1 lysed peptide-loaded Fas-deficient target cells derived from a patient with a homozygous Fas gene mutation, its cytotoxicity appeared to be mediated by a Fas-independent pathway. in addition, its cytotoxicity was only partially inhibited by treatment with concanamycin A and strontium ions, which are inhibitors of the perforin-based cytotoxic pathway. Although membrane-bound type of tumor necrosis factor-alpha (TNF-alpha) was expressed on HO-1. an anti-TNF-alpha antibody had no effect on HO-1-mediated cytotoxicity. HO-1 expressed mRNA for apoptosis-inducing mediators, including perforin, granzyme B, Fas ligand, TNF-alpha, and lymphotoxin; however, no DNA fragmentation was detected in target cells incubated with HO-1 by 5-[I-125]Iodo-2'-deoxyuridine release assay and agarose gel electrophoresis of DNA. Although it has been suggested that the Fas/Fas ligand system is the main pathway by which CD4(+) CTL-mediated cytotoxicity is exerted in murine systems, HO-1 produced peptide-specific and HLA-restricted cytotoxicity via a Fas-independent and nonapoptotic pathway. The present study thus describes a never mechanism of cytotoxicity mediated by CD4(+) CTL. (C) 1999 by The American Society of Hematology.
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收藏
页码:925 / 935
页数:11
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