Home LiteratureArticle Details
PMID: 9014814 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Release of preformed Fas ligand in soluble form is the major factor for activation-induced death of Jurkat T cells.

Immunology ·Vol. 89 ·No. 4 ·1996-12-00 ·Pages 511-7

Martínez-Lorenzo MJ, Alava MA, Anel A, Piñeiro A, Naval J

Abstract

Interaction of Fas/APO-1 (CD95) and its ligand (FasL) plays an important role in the activation-induced cell death (AICD) of T lymphocytes. In the present work, the contribution of soluble FasL to AICD of the human T-cell line Jurkat has been studied. Jurkat cells prestimulated with phytohaemagglutinin (PHA) induced the death of non-activated Jurkat cells, and also of L1210Fas, but not that of Fas-negative L1210 cells. Culture supernatants from prestimulated Jurkat cells were highly toxic to their non-activated counterparts. Time-course analysis revealed that PHA-stimulated Jurkat cells quickly release (less than 15 min) to the medium a toxic molecule following a biphasic pattern, with maximal cytotoxic activities at 1 hr and 7 hr after stimulation. The cytotoxic effect of those supernatants was prevented by the addition of a blocking anti-Fas monoclonal antibody, suggesting that PHA-stimulated Jurkat cells exert Fas-based cytotoxicity mainly through the release of soluble FasL. The constitutive intracellular expression of FasL in non-activated Jurkat cells and its release as a consequence of PHA activation were detected by immunostaining and immunoblotting using an anti-FasL antibody. These data indicate that, at least in Jurkat cells, AICD is mainly mediated by the rapid release of performed FasL in soluble form upon stimulation.

MeSH Terms
Apoptosis/immunology Blotting, Western Cytotoxicity Tests, Immunologic Fluorescent Antibody Technique Humans Jurkat Cells Ligands Lymphocyte Activation T-Lymphocytes/immunology fas Receptor/immunology
Chemicals
Ligands fas Receptor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Martínez-Lorenzo M J
Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences, University of Zaragoza, Spain.
Alava M A
Anel A
Piñeiro A
Naval J
References (33)
33 references, click to expand
  1. Transferrin receptors recycle to cis and middle as well as trans Golgi cisternae in Ig-secreting myeloma cells.
    J Cell Biol. 1986 Jul;103(1):277-86 PMID: 3013900
  2. Role of oxidative damage and IL-1 beta-converting enzyme-like proteases in Fas-based cytotoxicity exerted by effector T cells.
    Int Immunol. 1996 Jul;8(7):1173-83 PMID: 8757963
  3. Cytolysis by Ca-permeable transmembrane channels. Pore formation causes extensive DNA degradation and cell lysis.
    J Exp Med. 1989 Mar 1;169(3):765-77 PMID: 2538546
  4. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.
    J Exp Med. 1989 May 1;169(5):1747-56 PMID: 2469768
  5. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis.
    Nature. 1992 Mar 26;356(6367):314-7 PMID: 1372394
  6. Increased intracellular cyclic AMP inhibits inositol phospholipid hydrolysis induced by perturbation of the T cell receptor/CD3 complex but not by G-protein stimulation. Association with protein kinase A-mediated phosphorylation of phospholipase C-gamma 1.
    Biochem J. 1992 May 15;284 ( Pt 1):189-99 PMID: 1318020
  7. Induction of apoptosis by monoclonal antibody anti-APO-1 class switch variants is dependent on cross-linking of APO-1 cell surface antigens.
    J Immunol. 1992 Nov 15;149(10):3166-73 PMID: 1431095
  8. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity.
    J Exp Med. 1993 Jan 1;177(1):195-200 PMID: 7678113
  9. Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4409-13 PMID: 8506280
  10. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.
    Cell. 1993 Dec 17;75(6):1169-78 PMID: 7505205
  11. Purification and characterization of the Fas-ligand that induces apoptosis.
    J Exp Med. 1994 Mar 1;179(3):873-9 PMID: 7509364
  12. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand.
    Cell. 1994 Mar 25;76(6):969-76 PMID: 7511063
  13. Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated lymphocytes: a regulatory pathway?
    Eur J Immunol. 1994 Apr;24(4):923-7 PMID: 7512034
  14. T cell receptor-induced Fas ligand expression in cytotoxic T lymphocyte clones is blocked by protein tyrosine kinase inhibitors and cyclosporin A.
    Eur J Immunol. 1994 Oct;24(10):2469-76 PMID: 7523141
  15. Fas ligand mediates activation-induced cell death in human T lymphocytes.
    J Exp Med. 1995 Jan 1;181(1):71-7 PMID: 7528780
  16. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
    Nature. 1995 Feb 2;373(6513):438-41 PMID: 7530335
  17. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas.
    Nature. 1995 Feb 2;373(6513):441-4 PMID: 7530336
  18. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation.
    Nature. 1995 Feb 2;373(6513):444-8 PMID: 7530337
  19. TCR/CD3 coupling to Fas-based cytotoxicity.
    J Exp Med. 1995 Feb 1;181(2):781-6 PMID: 7530763
  20. The Fas death factor.
    Science. 1995 Mar 10;267(5203):1449-56 PMID: 7533326
  21. The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice.
    Immunity. 1994 Aug;1(5):365-71 PMID: 7533645
  22. The role of APO-1-mediated apoptosis in the immune system.
    Immunol Rev. 1994 Dec;142:175-91 PMID: 7535290
  23. Expression of the Fas ligand in cells of T cell lineage.
    J Immunol. 1995 Apr 15;154(8):3806-13 PMID: 7706720
  24. Expression of the functional soluble form of human fas ligand in activated lymphocytes.
    EMBO J. 1995 Mar 15;14(6):1129-35 PMID: 7536672
  25. A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation.
    Eur J Immunol. 1995 Jun;25(6):1749-54 PMID: 7615003
  26. Regulation of cell surface APO-1/Fas (CD95) ligand expression by metalloproteases.
    Eur J Immunol. 1995 Aug;25(8):2303-7 PMID: 7545118
  27. Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain.
    FEBS Lett. 1995 Oct 16;373(3):265-8 PMID: 7589480
  28. Activation-induced death of mature T cells in the regulation of immune responses.
    Curr Opin Immunol. 1995 Jun;7(3):382-8 PMID: 7546404
  29. Fas ligand-induced apoptosis as a mechanism of immune privilege.
    Science. 1995 Nov 17;270(5239):1189-92 PMID: 7502042
  30. Metalloproteinase-mediated release of human Fas ligand.
    J Exp Med. 1995 Dec 1;182(6):1777-83 PMID: 7500022
  31. Fas and FasL in the homeostatic regulation of immune responses.
    Immunol Today. 1995 Dec;16(12):569-74 PMID: 8579749
  32. Fas ligand in human serum.
    Nat Med. 1996 Mar;2(3):317-22 PMID: 8612231
  33. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.
    Cancer Res. 1988 Feb 1;48(3):589-601 PMID: 3335022
Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
DOI
10.1046/j.1365-2567.1996.d01-782.x
Published
1996-12-00
Pages
511-7
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1456570
Subset
IM
External Links
PubMed source DOI: 10.1046/j.1365-2567.1996.d01-782.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2