Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

CD95 ligand mediates T-cell receptor-induced apoptosis of a CD4+ CD8+ double positive thymic lymphoma

Oncogene volume 25, pages 7587–7596 (2006)Cite this article

Abstract

Tumors in the thymus can be of different cellular origin. Among the most common tumors are thymoma and lymphoma, which are derived from transformed thymic epithelial cells and transformed lymphocytes, respectively. Thymic lymphoma and their response to apoptotic stimuli are poorly characterized. Here, we analyse apoptosis events in the thymic lymphoma cell line Thy278, which expresses cell surface antigens characteristic of immature double positive thymocytes. Upon T-cell receptor (TCR)/CD3 stimulation, Thy278 cells die by apoptosis, similar as primary thymocytes during negative selection. Caspases are crucial for deletion of both Thy278 cells and normal thymocytes. Moreover, we show that deletion of primary thymocytes and Thy278 cells upon CD3 stimulation is considerably impaired by neutralizing CD95L antibody. Thus, our results not only demonstrate that TCR-induced apoptosis is still functional in transformed thymocytes, but also suggest that Thy278 cells are a helpful model for the molecular analysis of negative selection.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Aisenberg AC . (1993). J Clin Oncol 11: 2291–2294.

  • Alam A, Braun MY, Hartgers F, Lesage S, Cohen L, Hugo P et al. (1997). J Exp Med 186: 1503–1512.

  • Berg LJ, Fazekas de St Groth B, Ivars F, Goodnow CC, Gilfillan S, Garchon HJ et al. (1988). Mol Cell Biol 8: 5459–5469.

  • Boehm T, Rabbitts TH . (1989). FASEB J 3: 2344–2359.

  • Caserta TM, Smith AN, Gultice AD, Reedy MA, Brown TL . (2003). Apoptosis 8: 345–352.

  • Castro JE, Listman JA, Jacobson BA, Wang Y, Lopez PA, Ju S et al. (1996). Immunity 5: 617–627.

  • Chahinian AP . (2003). In: Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF et al. (eds). Cancer Medicine, vol. 2. BC Decker Inc.: Hamilton, London, pp 1467–1477.

    Google Scholar 

  • Chao DT, Korsmeyer SJ . (1998). Annu Rev Immunol 16: 395–419.

  • Clayton LK, Ghendler Y, Mizoguchi E, Patch RJ, Ocain TD, Orth K et al. (1997). EMBO J 16: 2282–2293.

  • Davis MM, Bjorkman PJ . (1988). Nature 334: 395–402.

  • Doerfler P, Forbush KA, Perlmutter RM . (2000). J Immunol 164: 4071–4079.

  • Fernandez E . (2000). Blood 95: 1356–1361.

  • Fischer U, Janicke RU, Schulze-Osthoff K . (2003). Cell Death Differ 10: 76–100.

  • Fischer U, Schulze-Osthoff K . (2005). Pharmacol Rev 57: 187–215.

  • Fuentes-Prior P, Salvesen GS . (2004). Biochem J 384: 201–232.

  • Geisler C . (2004). Crit Rev Immunol 24: 67–86.

  • Groves T, Katis P, Madden Z, Manickam K, Ramsden D, Wu G et al. (1995). J Immunol 154: 5011–5022.

  • Hanahan D, Weinberg RA . (2000). Cell 100: 57–70.

  • Hettmann T, DiDonato J, Karin M, Leiden JM . (1999). J Exp Med 189: 145–158.

  • Igney FH, Krammer PH . (2002). Nat Rev Cancer 2: 277–288.

  • Izquierdo M, Grandien A, Criado LM, Robles S, Leonardo E, Albar JP et al. (1999). EMBO J 18: 156–166.

  • Jiang X, Wang X . (2004). Annu Rev Biochem 73: 87–106.

  • Kaye J, Ellenberger DL . (1992). Cell 71: 423–435.

  • Kirchhoff S, Muller WW, Li-Weber M, Krammer PH . (2000). Eur J Immunol 30: 2765–2774.

  • Kovalik JP, Ansari B, Boothby M . (1996). J Immunol 157: 5290–5299.

  • Legembre P, Barnhart BC, Zheng L, Vijayan S, Straus SE, Puck J et al. (2004). EMBO Rep 5: 1084–1089.

  • Li H, Zhu H, Xu CJ, Yuan J . (1998). Cell 94: 491–501.

  • Los M, Wesselborg S, Schulze-Osthoff K . (1999). Immunity 10: 629–639.

  • Maeda T, Yamada Y, Moriuchi R, Sugahara K, Tsuruda K, Joh T et al. (1999). J Exp Med 189: 1063–1071.

  • Martin DA, Zheng L, Siegel RM, Huang B, Fisher GH, Wang J et al. (1999). Proc Natl Acad Sci USA 96: 4552–4557.

  • Matiba B, Mariani SM, Krammer PH . (1997). Semin Immunol 9: 59–68.

  • Moulian N, Berrih-Aknin S . (1998). Semin Immunol 10: 449–456.

  • Muschen M, Rajewsky K, Kronke M, Kuppers R . (2002). Trends Immunol 23: 75–80.

  • Namba T, Brunner NG, Grob D . (1978). Medicine (Baltimore) 57: 411–433.

  • Nishida T, Matsuki Y, Ono T, Oguma T, Tsujimoto K, Sato M et al. (2004). J Immunol 172: 6634–6641.

  • Peter ME, Krammer PH . (2003). Cell Death Differ 10: 26–35.

  • Rathmell JC, Thompson CB . (2002). Cell 109 (Suppl): S97–S107.

  • Reichmann E . (2002). Semin Cancer Biol 12: 309–315.

  • Rosai J, Levine GD . (1976). Atlas of Tumor Pathology. Armed Forces Institute of Pathology: Washington, DC.

    Google Scholar 

  • Sakahira H, Enari M, Nagata S . (1998). Nature 391: 96–99.

  • Sasada T, Reinherz EL . (2001). J Immunol 166: 2394–2403.

  • Schmitz I, Weyd H, Krueger A, Baumann S, Fas SC, Krammer PH et al. (2004). J Immunol 172: 2194–2200.

  • Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME . (1998). Eur J Biochem 254: 439–459.

  • Sidman CL, Marshall JD, Von Boehmer H . (1992). Eur J Immunol 22: 499–504.

  • Sohn D, Totzke G, Essmann F, Schulze-Osthoff K, Levkau B, Janicke RU . (2006). Mol Cell Biol 26: 1967–1978.

  • Starr TK, Jameson SC, Hogquist KA . (2003). Annu Rev Immunol 21: 139–176.

  • Venanzi ES, Benoist C, Mathis D . (2004). Curr Opin Immunol 16: 197–202.

  • Wadsworth S, Yui K, Siegel RM, Tenenholz DE, Hirsch JA, Greene MI . (1990). Eur J Immunol 20: 723–730.

  • Yefenof E . (1999). Adv Immunol 73: 511–539.

Download references

Acknowledgements

We thank D Scholtyssik for expert technical assistance, N Ueffing for help with FTOC and K Nienhaus for contributions to the early phase of this project. We are grateful to Dr A Kruisbeek (Amsterdam) for Thy278 cells, Dr H Wajant (Würzburg) for Flag-tagged CD95L and Dr EL Reinherz (Boston) for various reagents. We want to thank the people at the UKD animal facility for animal care. This work was funded by the Forschungskommission of the Faculty of Medicine, University of Düsseldorf.

Author information

Authors and Affiliations

  1. Institute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany

    I Schmitz, C Meyer & K Schulze-Osthoff

Authors
  1. I Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Schulze-Osthoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I Schmitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmitz, I., Meyer, C. & Schulze-Osthoff, K. CD95 ligand mediates T-cell receptor-induced apoptosis of a CD4+ CD8+ double positive thymic lymphoma. Oncogene 25, 7587–7596 (2006). https://doi.org/10.1038/sj.onc.1209741

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209741

Keywords

Search

Advanced search

Quick links