Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: A novel mechanism for the antitumor effects of type I IFNs.
J Exp Med
; 189(9): 1451-60, 1999 May 03.
Article
in En
| MEDLINE
| ID: mdl-10224285
ABSTRACT
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type II membrane proteins, which constitutes one component of T cell cytotoxicity. In this study, we investigated the expression and function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PBT cells did not express a detectable level of TRAIL on their surface, a remarkable TRAIL expression was rapidly induced on the surface of both CD4(+) and CD8(+) PBT cells upon stimulation with anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhancement of TRAIL expression was a unique feature of type I IFNs (IFN-alpha and IFN-beta), and neither type II IFN (IFN-gamma) nor various other cytokines enhanced TRAIL expression on anti-CD3-stimulated PBT cells. Type I IFNs have been used for clinical treatment of renal cell carcinomas (RCCs), and we found that most RCC cell lines were susceptible to TRAIL-induced apoptosis. Type I IFNs substantially augmented cytotoxic activity of anti-CD3-stimulated PBT cells against RCC cell lines in a TRAIL-dependent manner. These results indicate a unique feature of type I IFNs to regulate TRAIL-mediated T cell cytotoxicity, which may be involved in the antitumor effects of type I IFNs against various tumors.
Full text:
1
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
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CD4-Positive T-Lymphocytes
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Gene Expression Regulation
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Tumor Necrosis Factor-alpha
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Interferon-beta
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Interferon-alpha
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Apoptosis
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CD8-Positive T-Lymphocytes
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Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Exp Med
Year:
1999
Type:
Article
Affiliation country:
Japan