Abstract:
:Fas stimulation has been reported to promote the activation and proliferation of T lymphocytes, but the intracellular signalling pathways that mediate non-apoptotic responses to Fas are poorly defined. To distinguish between the activation signalling and the death-inducing pathway downstream of Fas, we generated a novel T cell line expressing a chimeric hCD8-FasC protein and found that stimulation with the anti-CD8 antibodies induced tyrosine phosphorylation of TCR-proximal proteins, activation of Raf-1/ERK, p38 and JNK, and increased expression of CD69, Fas, and Fas ligand. Stimulation of hCD8-FasC-induced activation of an atypical NF-kappaB pathway, partial cleavage of caspases, and increased expression of TRAF1, FLIP(L) and FLIP(S), thereby protecting T cells from FasL-mediated apoptosis. The proliferative response transmitted through hCD8-FasC chimeric receptors was converted into death signals when cells were stimulated, resulting in increased expression of IL-2 and Nur77 and increased caspase cleavage. Surprisingly, both the enhanced expression of FLIP(L) and FLIP(S) and the complete inhibition of FLIP(S) expression were functionally associated with cell death induction. These findings imply that Fas is able to trigger intracellular signalling events driving both apoptosis and activation of T cells but that cell fate is determined by quantitative and qualitative differences in intracellular signalling following Fas stimulation.
journal_name
Int J Hematoljournal_title
International journal of hematologyauthors
Shin MJ,Shim JH,Lee JY,Chae WJ,Lee HK,Morio T,Park JH,Chang EJ,Lee SKdoi
10.1007/s12185-010-0637-2subject
Has Abstractpub_date
2010-09-01 00:00:00pages
262-70issue
2eissn
0925-5710issn
1865-3774journal_volume
92pub_type
杂志文章abstract::The calcineurin inhibitors (CIs) cyclosporine A and tacrolimus are essential for graft-versus-host disease prophylaxis but are associated with adverse effects, including neurotoxicity. We report a case of irreversible CI-induced neuropathic pain following allogeneic hematopoietic stem cell transplantation. The patient...
journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
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