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PMID: 10224285 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

The Journal of experimental medicine ·Vol. 189 ·No. 9 ·1999-05-03 ·Pages 1451-60

Kayagaki N, Yamaguchi N, Nakayama M, Eto H, Okumura K, Yagita H

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.

MeSH Terms
Antineoplastic Agents/metabolism,pharmacology Apoptosis Apoptosis Regulatory Proteins CD3 Complex/metabolism CD4-Positive T-Lymphocytes/metabolism CD8-Positive T-Lymphocytes/metabolism Cytokines/metabolism,pharmacology Cytotoxicity, Immunologic Gene Expression Regulation/drug effects Humans Interferon-alpha/metabolism,pharmacology Interferon-beta/metabolism,pharmacology Jurkat Cells Ligands Membrane Glycoproteins/genetics Receptor-CD3 Complex, Antigen, T-Cell/metabolism TNF-Related Apoptosis-Inducing Ligand Transcription, Genetic/drug effects Tumor Necrosis Factor-alpha/genetics
Chemicals
Antineoplastic Agents Apoptosis Regulatory Proteins CD3 Complex Cytokines Interferon-alpha Ligands Membrane Glycoproteins Receptor-CD3 Complex, Antigen, T-Cell TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Tumor Necrosis Factor-alpha Interferon-beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kayagaki N
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
Yamaguchi N
Nakayama M
Eto H
Okumura K
Yagita H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.189.9.1451
Published
1999-05-03
Pages
1451-60
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193058
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.189.9.1451 PMC Full Text View journal details
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