• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Mar 15, 1997; 99(6): 1173–1178.
PMCID: PMC507930

Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain?


Astrocytomas are among the most common brain tumors that are usually fatal in their malignant form. They appear to progress without significant impedance from the immune system, despite the presence of intratumoral T cell infiltration. To date, this has been thought to be the result of T cell immunosuppression induced by astrocytoma-derived cytokines. Here, we propose that cell contact-mediated events also play a role, since we demonstrate the in vivo expression of Fas ligand (FasL/CD95L) by human astrocytoma and the efficient killing of Fas-bearing cells by astrocytoma lines in vitro and by tumor cells ex vivo. Functional FasL is expressed by human, mouse, and rat astrocytoma and hence may be a general feature of this nonlymphoid tumor. In the brain, astrocytoma cells can potentially deliver a death signal to Fas+ cells which include infiltrating leukocytes and, paradoxically, astrocytoma cells themselves. The expression of FasL by astrocytoma cells may extend the processes that are postulated to occur in normal brain to maintain immune privilege, since we also show FasL expression by neurons. Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system.

Full Text

The Full Text of this article is available as a PDF (289K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barker CF, Billingham RE. Immunologically privileged sites. Adv Immunol. 1977;25:1–54. [PubMed]
  • Fabry Z, Raine CS, Hart MN. Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Today. 1994 May;15(5):218–224. [PubMed]
  • Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992 Dec;13(12):507–512. [PubMed]
  • Fontana A, Kristensen F, Dubs R, Gemsa D, Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed]
  • Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, Heid I, Fontana A. Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J Immunol. 1989 Nov 15;143(10):3222–3229. [PubMed]
  • Rich S, Seelig M, Lee HM, Lin J. Transforming growth factor beta 1 costimulated growth and regulatory function of staphylococcal enterotoxin B-responsive CD8+ T cells. J Immunol. 1995 Jul 15;155(2):609–618. [PubMed]
  • Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S. TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol. 1995 Jul 1;155(1):325–332. [PubMed]
  • Kuppner MC, Hamou MF, de Tribolet N. Immunohistological and functional analyses of lymphoid infiltrates in human glioblastomas. Cancer Res. 1988 Dec 1;48(23):6926–6932. [PubMed]
  • Rossi ML, Hughes JT, Esiri MM, Coakham HB, Brownell DB. Immunohistological study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol. 1987;74(3):269–277. [PubMed]
  • Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. [PubMed]
  • Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. [PubMed]
  • Lynch DH, Ramsdell F, Alderson MR. Fas and FasL in the homeostatic regulation of immune responses. Immunol Today. 1995 Dec;16(12):569–574. [PubMed]
  • Lowin B, Hahne M, Mattmann C, Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature. 1994 Aug 25;370(6491):650–652. [PubMed]
  • Kägi D, Vignaux F, Ledermann B, Bürki K, Depraetere V, Nagata S, Hengartner H, Golstein P. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528–530. [PubMed]
  • Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. [PubMed]
  • Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995 Nov 17;270(5239):1189–1192. [PubMed]
  • Van Meir E, Sawamura Y, Diserens AC, Hamou MF, de Tribolet N. Human glioblastoma cells release interleukin 6 in vivo and in vitro. Cancer Res. 1990 Oct 15;50(20):6683–6688. [PubMed]
  • Serano RD, Pegram CN, Bigner DD. Tumorigenic cell culture lines from a spontaneous VM/Dk murine astrocytoma (SMA). Acta Neuropathol. 1980;51(1):53–64. [PubMed]
  • Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol. 1993 Jul;3(3):255–268. [PubMed]
  • Hahne M, Peitsch MC, Irmler M, Schröter M, Lowin B, Rousseau M, Bron C, Renno T, French L, Tschopp J. Characterization of the non-functional Fas ligand of gld mice. Int Immunol. 1995 Sep;7(9):1381–1386. [PubMed]
  • Takahashi T, Tanaka M, Inazawa J, Abe T, Suda T, Nagata S. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994 Oct;6(10):1567–1574. [PubMed]
  • Sarmiento M, Dialynas DP, Lancki DW, Wall KA, Lorber MI, Loken MR, Fitch FW. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. [PubMed]
  • Kayagaki N, Kawasaki A, Ebata T, Ohmoto H, Ikeda S, Inoue S, Yoshino K, Okumura K, Yagita H. Metalloproteinase-mediated release of human Fas ligand. J Exp Med. 1995 Dec 1;182(6):1777–1783. [PMC free article] [PubMed]
  • Bordier C. Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem. 1981 Feb 25;256(4):1604–1607. [PubMed]
  • Hahne M, Renno T, Schroeter M, Irmler M, French L, Bornard T, MacDonald HR, Tschopp J. Activated B cells express functional Fas ligand. Eur J Immunol. 1996 Mar;26(3):721–724. [PubMed]
  • Matzinger P. The JAM test. A simple assay for DNA fragmentation and cell death. J Immunol Methods. 1991 Dec 15;145(1-2):185–192. [PubMed]
  • Suda T, Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med. 1994 Mar 1;179(3):873–879. [PMC free article] [PubMed]
  • Weller M, Frei K, Groscurth P, Krammer PH, Yonekawa Y, Fontana A. Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J Clin Invest. 1994 Sep;94(3):954–964. [PMC free article] [PubMed]
  • French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Müller C, Tschopp J. Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol. 1996 Apr;133(2):335–343. [PMC free article] [PubMed]
  • Glass A, Walsh CM, Lynch DH, Clark WR. Regulation of the Fas lytic pathway in cloned CTL. J Immunol. 1996 May 15;156(10):3638–3644. [PubMed]
  • Iwai K, Miyawaki T, Takizawa T, Konno A, Ohta K, Yachie A, Seki H, Taniguchi N. Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils. Blood. 1994 Aug 15;84(4):1201–1208. [PubMed]
  • Smyth MJ, Strobl SL, Young HA, Ortaldo JR, Ochoa AC. Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol. 1991 May 15;146(10):3289–3297. [PubMed]
  • Streilein JW. Unraveling immune privilege. Science. 1995 Nov 17;270(5239):1158–1159. [PubMed]
  • O'Connell J, O'Sullivan GC, Collins JK, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 1996 Sep 1;184(3):1075–1082. [PMC free article] [PubMed]
  • Hahne M, Rimoldi D, Schröter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Lienard D, et al. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996 Nov 22;274(5291):1363–1366. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...