Skip to main content
SpringerLink
Log in

Programmed cell death: the influence of CD40, CD95 (Fas or Apo-I) and their ligands

  • Review
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Programmed cell death (PCD) or apoptosis is a process whereby developmental or environmental stimuli activate a specific series of events that culminate in cell death. PCD is essential for normal development and abnormality in the process can lead to defects ranging from embryonic lethality and tissue-specific perturbation of postnatal development to a high susceptibility to malignancy. Therapeutics that modulate the regulation of PCD may provide a new opportunity for the treatment of the PCD related diseases and cancer. CD40 and CD95 (Fas/Apo-I) are transmembrane proteins of the nerve growth factor/tumour necrosis factor α receptor superfamily. The death signal of PCD occurs when the CD95 receptor on the cell surface binds to the CD95 ligand (CD95L) or to the anti-CD95 monoclonal antibody (mAb). In contrast, PCD could be inhibited by the survival signal mediated from the binding of the CD40 receptor to the CD40 ligand (CD40L) or to the anti-CD40 mAb. In this review, the interaction of CD40/CD40L and CD95/CD95L on PCD in normal and malignant cells is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Krammer PH, Behrmann I, Daniel P, Dhein J, Debatin K. Regulation of apoptosis in the immune system.Curr Opin Immunol 1994;6: 279–289.

    Article  CAS  PubMed  Google Scholar 

  2. MacLennan ICM. Germinal centers.Annu Rev Immunol 1994;12: 117–139.

    Article  CAS  PubMed  Google Scholar 

  3. Gordon J, Katira A, Holder M, MacDonald I, Pound J. Central role of CD40 and its ligand in B lymphocyte response to T dependent antigens.Cell Mol Biol 1994;40: 1–12.

    CAS  PubMed  Google Scholar 

  4. Öhm Aet al. Purification and molecular cloning of the Apo-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily.J Biol Chem 1992;267: 10709–10715.

    Article  Google Scholar 

  5. Lagresle C, Bella C, Daniel P, Krammer PH, Defrance T. Regulation of germinal center B cell differentiation. Role of the human Apo1/Fas (CD95) molecule.J Immunol 1995;154: 5746–5756.

    Article  CAS  PubMed  Google Scholar 

  6. Kägi Det al. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity.Science 1994;265: 528–530.

    Article  PubMed  Google Scholar 

  7. Ramsdell Fet al. Differential ability of Th1 and Th2 T cells to undergo activation induced cell death.Int Immunol 1994;6: 1545–1553.

    Article  CAS  PubMed  Google Scholar 

  8. Hahn S, Gehri R, Erb P. Mechanism and biological significance of CD4 mediated cytotoxicity.Immunol Rev 1995;146: 57–79.

    Article  CAS  PubMed  Google Scholar 

  9. Sad Set al. Cytotoxic and weak CD40 ligand expression of CD8+ type 2 cytotoxic T cells restricts their potential B cell helper activity.Eur J Immunol 1997;27: 914–922.

    Article  CAS  PubMed  Google Scholar 

  10. Vergelli Met al. Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand- mediated pathways for target cell lysis.J Immunol 1997;158: 2756–2761.

    Article  CAS  PubMed  Google Scholar 

  11. Rensing-Ehl Aet al. Local Fas/Apo-1 (CD95) ligand-mediated tumor cell killingin vivo.Eur J Immunol 1995;25: 2253–2258.

    Article  CAS  PubMed  Google Scholar 

  12. Nagata S, Goldstein P. The Fas death factor.Science 1995;267: 1449–1456.

    Article  CAS  PubMed  Google Scholar 

  13. Russell J, Rush B, Weaver C, Wang R. Mature T cells of autoimmunelpr/lpr mice have a defect in antigen-stimulated suicide.Proc Natl Acad Sci USA 1993;90: 4409–4413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Reap E, Leslie D, Abrahams M, Eisenberg R, Cohen P. Apoptosis abnormalities of splenic lymphocytes in autoimmunelpr andgld mice.J Immunol 1995;154: 936–943.

    Article  CAS  PubMed  Google Scholar 

  15. Stamenkovic I, Clark E, Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas.EMBO J 1989;8: 1403–1410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Uckum Fet al. Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover and multiple previously unidentified serine thyreonine-specific protein kinases by the pan-B cell receptor CD40/Bp50 at discrete development stages of human B cell ontogeny.J Biol Chem 1991;266: 17478–17485.

    Article  Google Scholar 

  17. Schriever Fet al. Isolation human follicular dendritic cells display a unique antigenic phenotype.J Exp Med 1989;169: 2043–2058.

    Article  CAS  PubMed  Google Scholar 

  18. Liu Yet al. Mechanism of antigen-driven selection in germinal centres.Nature 1989;342: 929–931.

    Article  CAS  PubMed  Google Scholar 

  19. Banchereau J, de Paoli P, Valle A, Garcia E, Rousset F. Long term human B cell lines dependent on Interleukin-4 and antibody to CD40.Science 1991;251: 70–72.

    Article  CAS  PubMed  Google Scholar 

  20. Armitage Ret al. Molecular and biological characterization of a murine ligand for CD40.Nature 1992;357: 80–82.

    Article  CAS  PubMed  Google Scholar 

  21. Banchereau Jet al. The CD40 antigen and its ligand.Ann Rev Immunol 1994;12: 881–922.

    Article  CAS  Google Scholar 

  22. Faris M, Gaskin F, Parsons J, Fu S. CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase lyn, fyn and syk and the appearance of a 28-kD tyrosine-phosphorylated protein.J Exp Med 1994;179: 1923–1931.

    Article  CAS  PubMed  Google Scholar 

  23. Lederman S, Yellin MJ, Cleary AM, Pernis A, Inghirami G, Cohn LE, Covey LR, Lee JJ, Rothman P, Chess L. T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death.J Immunol 1994;152: 2163–2171.

    Article  CAS  PubMed  Google Scholar 

  24. Spriggs M, Fanslow R, Armitage R, Belmont J. The biology of the human ligand for CD40.J Clin Immunol 1993;13: 373–380.

    Article  CAS  PubMed  Google Scholar 

  25. Foy Tet al. GP 39-CD40 interactions are essential for germinal center formation and the development of B cell memory.J Exp Med 1994;180: 157–163.

    Article  CAS  PubMed  Google Scholar 

  26. Kindler V, Zubler R. Memory but not naive, peripheral blood B lymphocytes differentiate into Ig-secreting cells after CD40 ligation and costimulation with IL4 and the differentiation factors IL2, IL10 and IL3.J Immunol 1997;159: 2084–2090.

    Article  Google Scholar 

  27. Lagresle C, Mondiere P, Bella C, Krammer PH, Defrance T. Concurrent engagement of CD40 and the antigen receptor protect naive and memory human B cells from Apo-1/Fas mediated apoptosis.J Exp Med 1996;183: 1377–1388.

    Article  CAS  PubMed  Google Scholar 

  28. Schattner Eet al. CD40 ligation induces Apo-I/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway.J Exp Med 1995;182: 1557–1565.

    Article  CAS  PubMed  Google Scholar 

  29. DiSanto J, Bonnefoy J, Gauchat J, Fisher A, de Saint Basile G. CD40 ligand mutation in X-linked immunodeficiency with hyper IgM.Nature (Lond.) 1993;361: 541–543.

    Article  CAS  PubMed  Google Scholar 

  30. Zang L, Miller R, Zang J. Characterization of apoptosis-resistant antigen-specific T cellsin vivo.J Exp Med 1996;183: 2065–2070.

    Article  Google Scholar 

  31. Mapara Met al. Apo-I mediated apoptosis or proliferation in human chronic B lymphocytic leukaemia: correlation with Bcl-2 oncogene expression.Eur J Immunol 1993;23: 702–708.

    Article  CAS  PubMed  Google Scholar 

  32. Shima Y, Nishimoto N, Yoshizaki K, Kishimoto T. Fas antigen/Apo-I (CD95) expression on myeloma cells.Leukaemia and Lymphoma 1996;23: 521–531.

    Article  CAS  Google Scholar 

  33. Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S. Essential roles of Fas ligand in the development of hepatitis.Nature Med 1997;3: 409–413.

    Article  CAS  PubMed  Google Scholar 

  34. Notarangelo L, Duse M, Ugazio A. Immunodeficiency with hyper-IgM (HIM).Immunodefic Rev 1992;3: 101–121.

    CAS  PubMed  Google Scholar 

  35. Fisher Get al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome.Cell 1995;81: 935–946.

    Article  CAS  PubMed  Google Scholar 

  36. Rieux-Laucat Fet al. Mutations in Fas associated with human lymphoproliferation syndrome and autoimmunity.Science (Wash, DC) 1995;268: 1347–1349.

    Article  CAS  PubMed  Google Scholar 

  37. Weller Met al. Anti-Fas/Apo-I antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines.J Clin Invest 1994;94: 954–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Strand Set al. Lymphocyte apoptosis induced by CD95 (Apo1/Fas) ligand-expressing tumor cells—a mechanism of immune evasion?.Nature Med 1996;2: 1361–1366.

    Article  CAS  PubMed  Google Scholar 

  39. O'Connell J, O'Sullivan G, Collins J, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand.J Exp Med 1996;184: 1075–1082.

    Article  CAS  PubMed  Google Scholar 

  40. Hahne Met al. Melanoma cell expression of Fas (Apo-1/CD95) ligand: implications of tumor immune escape.Science 1996;274: 1363–1366.

    Article  CAS  PubMed  Google Scholar 

  41. Villunger Aet al. Constitutive expression of Fas (Apo-1/CD95) ligand on multiple myeloma cells: a potential mechanism of tumor-induced suppression of immune surveillance.Blood 1997;90: 12–20.

    Article  CAS  PubMed  Google Scholar 

  42. Sato Ket al. An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand.Br J Haematol 1996;94: 379–382.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immune and Gene Therapy Laboratory, Department of Oncology, Radiumhemmet, Karolinska Hospital, S-17176, Stockholm, Sweden

    N Laytragoon-Lewin

Authors
  1. N Laytragoon-Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Laytragoon-Lewin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laytragoon-Lewin, N. Programmed cell death: the influence of CD40, CD95 (Fas or Apo-I) and their ligands. Med Oncol 15, 15–19 (1998). https://doi.org/10.1007/BF02787339

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02787339

Keywords

Search

Navigation