Skip to main content
SpringerLink
Log in

Management of Murine Lupus by Correction of Fas and Fas Ligand-Induced Apoptosis

Therapeutic Rationale and Strategies

  • Chapter
Lupus

Part of the book series: Contemporary Immunology ((CONTIM))

Abstract

Identification of mutations of fas and fas ligand (fasL) genes in murine models of autoimmune disease has provided an important experimental tool for the analysis of tolerance and autoimmune disease. Mutations of fasL and fas genes are not a common cause of autoimmune disease in humans, although a mutation of the fas gene has been associated with autoimmune lymphoproliferative syndrome (1–5), and we have described a mutation of the fasL gene in one patient with SLE (6). Furthermore, accumulating evidence suggests that dysregulation of apoptosis or altered levels of expression of FasL and Fas plays an important role in the pathogenesis of diseases associated with immune regulation (6–11). Fas apoptosis appears to be the primary mechanism for elimination of autoreactive T cells outside the thymus. FasL regulation is tightly controlled, and specific cells and transcription factors have been identified that play a role in this process. Further investigations of Fas/FasL regulation should allow development of strategies to restore T-cell tolerance in autoimmune situations. The first part of this chapter uses Fas/FasL as an example to demonstrate the importance of apoptosis in the regulation of immune homeostasis. The second part of this chapter follows the footsteps of investigators in this field to understand how one can apply modern technology to understand mechanisms associated with genetic defect-related autoimmune disease and to develop strategies to overcome these defects.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fisher, G. H., Rosenberg, F. J., Straus, S. E., Dale, L., et al. (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81, 935–946.

    Article  PubMed  CAS  Google Scholar 

  2. Rieux-Laucat, F., LeDeist, F., Hivroz, C., Roberts, I. A., et al. (1995) Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 263, 1347–1349.

    Article  Google Scholar 

  3. Fuss, I. J., Strober, W., Dale, J. K., et al. (1997) Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity. J. Immunol. 158, 1912–1918.

    PubMed  CAS  Google Scholar 

  4. Sneller, M. C., Wang, J., Dale, J. K., et al. (1997) Clinical, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Blood 89, 1341–1348.

    PubMed  CAS  Google Scholar 

  5. Drappa, J., Vaishnaw, A. K., Sullivan, K. E., et al. (1996) Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity N. Engl. J. Med. 335, 1643–1649.

    Article  PubMed  CAS  Google Scholar 

  6. Wu, J., Wilson, J., He, J., Xiang, L., Schur, P. H., and Mountz, J. D. (1996) Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J. Clin. Invest. 98, 1107–1113.

    Article  PubMed  CAS  Google Scholar 

  7. Mountz, J. D., Wu, J:, Cheng, J., and Zhou, T. (1994) Autoimmune disease: a problem of defective apoptosis. Arthritis Rheum. 37, 1415–1420.

    Google Scholar 

  8. Elkon, K. B. (1994) Apoptosis in SLE—too little or too much? Clin. Exp. Rheumatol. 12, 553–559.

    PubMed  CAS  Google Scholar 

  9. Rose, L. M., Latchman, D. S., and Isenberg, D. A. (1994) Bc1–2 and Fas, molecules which influence apoptosis: a possible role in systemic lupus erythematosus? Autoimmunity 17, 271–278.

    Article  PubMed  CAS  Google Scholar 

  10. Ohsako, S., Hara, M., Harigai, M., Fukasawa, C., and Kashiwazaki, S. (1995) Expression and function of Fas antigen and bc1–2 in human systemic lupus erythematosus lymphocytes. Clin. Immunol. Immunopathol. 73, 109–114.

    Article  Google Scholar 

  11. Mysler, E., Bini, P., Drappa, J., Ramos, P., Friedman, S. M., Krammer, P. H., and Elkon, K. B. (1994) The apoptosis-1/Fas protein in human systemic lupus erythematosus. J. Clin. Invest. 93, 1029–1034.

    Article  PubMed  CAS  Google Scholar 

  12. Andrews, B. S., Eisenberg, R. A., Theofilopoulos, A. N., Izui, S., Wilson, C. B., McConahey, P. J., Murphy, E. D., Roths, J. B., and Dixon, F. J. (1978) Spontaneous murine lupus-like syndrome: clinical and immunopathological manifestations in several strains. J. Exp. Med. 148, 1198–1207.

    Article  PubMed  CAS  Google Scholar 

  13. Dixon, F. J. (1982) Murine lupus—an overview. Arthritis Rheum. 25, 721–725.

    Article  PubMed  CAS  Google Scholar 

  14. Morse, H. C. III, Davidson, W. F., Yetter, R. A., Murphy, E. D., Roth, J. B., and Coffman, R. L. (1982) Abnormalities induced by the mutant gene 1pr: expansion of a unique lymphocyte subset. J. Immunol. 129, 2612–2620.

    PubMed  Google Scholar 

  15. Singer, P. and Theofilopoulos, A. N. (1990) Novel origin of 1pr and gld cells and possible implications in autoimmunity. J. Autoimmun. 3, 123–135.

    Article  PubMed  CAS  Google Scholar 

  16. Nemanzee, D. A., Studer, S., Steinmetz, M., Dembic, Z., and Kiefer, M. (1985) The lymphoproliferating cells of MRL-1pr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. Eur. J. Immunol. 15, 760–764.

    Article  Google Scholar 

  17. Tarkowski, A., Jonnson, R., Holmdahl, R., and Klareskog, L. (1987) Immunohistochemical characterization of synovial cells in arthritic MRL-1pr/lpr mice. Arthritis Rheum. 30, 75–82.

    Article  PubMed  CAS  Google Scholar 

  18. Alexander, E. L., Moyer, C., Travlos, G. S., Roths, J. B., and Murphy, E. D. (1985) Two histopathological types of inflammatory vascular disease in MRL/Mp autoimmune mice: model of human vasculitis in connective tissue disease. Arthritis Rheum. 28, 1146–1955.

    Article  PubMed  CAS  Google Scholar 

  19. Spurney, R. F., Ruiz, P., Pisetsky, D. S., and Coffman, T. M. (1991) Enhanced renal leukotriene production in murine lupus: role of lipoxygenase metabolites. Kidney Int. 39, 95–102.

    Article  PubMed  CAS  Google Scholar 

  20. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314–317.

    Article  PubMed  CAS  Google Scholar 

  21. Watanabe-Fukunaga, R., Brannan, C. I., Itoh, N., Yonehara, S., Copeland, N. G., Jenkins, N. A., and Nagata, S. (1992) The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J. Immunol. 148, 1274.

    PubMed  CAS  Google Scholar 

  22. Inazawa, J., Itoh, N., Abe, T., and Nagata, S. (1992) Assignment of the human Fas antigen gene (FAS) to 10g24.1. Genomics 14, 821–822.

    Article  PubMed  CAS  Google Scholar 

  23. Watanabe, T., Sakai, Y., Miyawaki, S., Shimizu, A., Koiwai, O., and Ohno, K. (1991) A molecular genetic linkage map of mouse chromosome 19, including the 1pr, Ly-44, and Tdt genes. Biochem. Genetics 29, 325–335.

    Article  CAS  Google Scholar 

  24. Adachi, M., Watanabe-Fukunaga, R., and Nagata, S. (1993) Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of 1pr mice. Proc. Natl. Acad. Sci. USA 90, 1756.

    Article  PubMed  CAS  Google Scholar 

  25. Chu, J-L., Drappa, J., Parnassa, A. P., and Elkon, K. B. (1993) The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J. Exp. Med. 178, 723.

    Article  CAS  Google Scholar 

  26. Kobayashi, S., Hirano, T., Kakinuma, M., and Uede, T. (1993) Transcriptional repression and differential splicing of Fas mRNA by early transposon (ETn) insertion in autoimmune 1pr mice. Biochem. Biophy. Res. Commun. 191, 617–624.

    Article  CAS  Google Scholar 

  27. Wu, J., Zhou, T., He, J., and Mountz, J. D. (1993) Murine autoimmune disease due to integration of an endogenous retrovirus in an apoptosis gene. J. Exp. Med. 178, 461–468.

    Article  PubMed  CAS  Google Scholar 

  28. Mountz, J. D., Mushinski, J. F., Mark, G. E., and Steinberg, A. D. (1985) Oncogene expression in autoimmune mice. J. Mol. Cell. Immunol. 2, 121–131.

    PubMed  CAS  Google Scholar 

  29. Allen, R. D., Marshell, J. D., Roths, J. B., and Sidman, C. D. (1990) Differences defined by bone marrow transplantation suggest that 1pr and gld are mutations of genes encoding an interacting pair of molecules. J. Exp. Med. 172, 1367–1375.

    Article  PubMed  CAS  Google Scholar 

  30. Suda, T., Okazaki, T., Naito, Y., et al. (1995) Expression of the Fas ligand in cells of T cell lineage. J. Immunol. 154, 3806–3813.

    PubMed  CAS  Google Scholar 

  31. Suda, T. and Nagata, S. (1994) Purification and characterization of the Fas-ligand that induces apoptosis. J. Exp. Med. 179, 873–879.

    Article  PubMed  CAS  Google Scholar 

  32. Takahashi, T., Tanaka, M., Brannan, C. I., Jenkins, N.A., Copeland, N. G., Suda, T., and Nagata, S. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76, 969–976.

    Article  PubMed  CAS  Google Scholar 

  33. Lynch, D. H., Watson, M. L., Alderson, M. R., Baum, P. R., Miller, R. E., Tough, T., Gibson, M., Davis-Smith, T., Smith, C. A., Hunter, K., Bhat, D., Din, W., Goodwin, R. G., and Seldin, M. F. (1994) The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Immunity 1, 131–136.

    Article  PubMed  CAS  Google Scholar 

  34. Ramsdell, F., Seaman, M. S., Miller, R. E., Tough, T. W., Alderson, M. R., and Lynch, D. H. (1994) Gld/gld mice are unable to express a functional ligand for Fas. Eur. J. Immunol. 24, 928–933.

    CAS  Google Scholar 

  35. Takahashi, T., Tanaka, M., Inazawa, J., Abe, T., Suda, T., and Nagata, S. (1994) Human Fas ligand: gene structure, chromosomal location and species specificity. Int. Immunol. 6, 1567–1574.

    Article  PubMed  CAS  Google Scholar 

  36. Peitsch, M. C. and Tschopp, J. (1995) Comparative molecular modeling of the Fas-ligand and other members of the TNF family. Mol. Immunol. 32, 761–772.

    Article  PubMed  CAS  Google Scholar 

  37. Smith, C. A., Farrah, T., and Goodwin, R. G. (1994) The TNF receptor superfamily of cellular and viral proteins: activation, co-stimulation, and death. Cell 76, 959.

    Article  PubMed  CAS  Google Scholar 

  38. Tanaka, M., Suda, T., Takahashi, T., and Nagata, S. (1995) Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 14, 1129–1135.

    PubMed  CAS  Google Scholar 

  39. Kayagaki, N., Kawasaki, A., Ebata, T., et al. (1995) Metalloproteinase-mediated release of human Fas ligand. J. Exp. Med. 182, 1777–1783.

    Article  PubMed  CAS  Google Scholar 

  40. Mariani, S. M., Matiba, B., Baumler, C., and Krammer, P. H. (1995) Regulation of cell surface APO-1/Fas (CD95) ligand expression by metalloproteinase. Eur. J. Immunol. 25, 2303–2307.

    Article  PubMed  CAS  Google Scholar 

  41. Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., et al. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14, 5579–5588.

    PubMed  CAS  Google Scholar 

  42. Stanger, B. Z., Leder, P., Lee, T. H., Kim, E., and Seed, B. (1995) RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81, 513–523.

    Article  PubMed  CAS  Google Scholar 

  43. Chinnaiyan, A. M., O’Rourke, K., Tewari, M., and Dixit, V. M. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81, 505–512.

    Article  PubMed  CAS  Google Scholar 

  44. Boldin, M. P., Varfolomeev, E. E., Pancer, Z., Mett, I. L., Camonis, J. H., and Wallach, D. (1995) A novel protein that interacts with the death domain of Fas/APO-1 contains a sequence motif related to the death domain. J. Biol. Chem. 270, 7795–7798.

    Article  PubMed  CAS  Google Scholar 

  45. Glass, A., Walsh, C. M., Lynch, D. H., and Clark, W. R. (1996) Regulation of the Fas lytic pathway in cloned CTL. J. Immunol. 156, 3638–3644.

    PubMed  CAS  Google Scholar 

  46. Ramsdell, F., Seaman, M. S., Miller, R. E., Picha, K. S., Kennedy, M. K., and Lynch, D. H. (1994) Differential ability of Thl and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. Int. Immunol. 6, 1545–1553.

    Article  PubMed  CAS  Google Scholar 

  47. Suda, T., Takahashi, T., Golstein, P., and Nagata, S. (1993) Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75, 1169–1178.

    Article  PubMed  CAS  Google Scholar 

  48. Hahn, S., Stalder, T., Wernli, M., Bergin, D., et al. (1995) Down-modulation of CD4+ T helper type 2 and type 0 cells by T helper type 1 cells via Fas/Fas-ligand interaction. Eur. J. Immunol. 25, 2679–2685.

    Article  PubMed  CAS  Google Scholar 

  49. Hanabuchi, S., Koyanagi, M., Kawasaki, A., et al. (1994) Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity. Proc. Natl. Acad. Sci. USA 91, 4930–4934.

    Article  PubMed  CAS  Google Scholar 

  50. Anel, A., Simon, A. K., Auphan, N., Buferne, M., et al. (1995) Two signaling pathways can lead to Fas ligand expression in CD8+ cytotoxic T lymphocyte clones. Eur. J. Immunol. 25, 3381–3387.

    Article  PubMed  CAS  Google Scholar 

  51. Hahne, M., Renno, T., Schroeter, M., Irmler, M., et al. (1996) Activated B cells express functional Fas ligand. Eur. J. Immunol. 26, 721–724.

    Article  PubMed  CAS  Google Scholar 

  52. Montel, A. H., Bochan, M. R., Goebel, W. S., and Brahmi, Z. (1995) Fas-mediated cytotoxicity remains intact in perforin and granzyme B antisense transfectants of a human NK-like cell line. Cell Immunol. 165, 312–317.

    Article  PubMed  CAS  Google Scholar 

  53. Arase, H., Arase, N., Kobayashi, Y., et al. (1994) Cytotoxicity of fresh NKl.1+ T cell receptor aß+ thymocytes against a CD4+8+ thymocyte population associated with intact Fas antigen expression on the target. J. Exp. Med. 180, 423–432.

    Article  PubMed  CAS  Google Scholar 

  54. Arase, H., Arase, N., and Saito, T. (1995) Fas-mediated cytotoxicity by freshly isolated natural killer cells. J. Exp. Med. 181, 1235–1238.

    Article  PubMed  CAS  Google Scholar 

  55. Badley, A. D., McElhinny, J. A., Leibson, P. J., et al. (1996) Upregulation of Fas ligand expression by human immunodeficiency virus in human macrophages mediates apoptosis of uninfected T lymphocytes. J. Virol. 70, 199–206.

    PubMed  CAS  Google Scholar 

  56. Ferguson, T. A. and Griffith, T. S. (1997) A vision of cell death: insight into immune privilege. Immunol. Rev. 156, 167–184.

    Article  PubMed  CAS  Google Scholar 

  57. Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A., and Duke, R. C. (1995) A role for CD95 ligand in preventing graft rejection. Nature 377, 630–632.

    Article  PubMed  CAS  Google Scholar 

  58. Chinnaiyan, A. M. and Dixit, V. M. (1997) Portrait of an executioner: the molecular mechanism of Fas/APO-1-induced apoptosis. Semin. Immunol. 9, 69–76.

    Article  PubMed  CAS  Google Scholar 

  59. Wallach, D. (1997) Cell death induction by TNF: a matter of self control. TIBS 22, 107–109.

    PubMed  CAS  Google Scholar 

  60. Yuan, J. (1997) Transducing signals of life and death. Curr. Opin. Cell Biol. 9, 247–251.

    Article  PubMed  CAS  Google Scholar 

  61. Chinnaiyan, A. M., Tepper, C. G., Seldin, M. F., O’Rourke, K., Kischkel, F. C., Hellbardt, S., Krammer, P. H., Peter, M. E., and Dixit, V. M. (1996) FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J. Biol. Chem. 271, 4961–4965.

    Article  PubMed  CAS  Google Scholar 

  62. Boldin, M. P., Goncharov, T. M., Goltsev, Y. V., and Wallach, D. (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease in Fas/APO-1 and TNF receptor-induced cell death. Cell 85, 803–815.

    Article  PubMed  CAS  Google Scholar 

  63. Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., et al. (1995) Cytotoxicitydependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14, 5579–5588.

    PubMed  CAS  Google Scholar 

  64. Hsu, H., Xiong, J., and Goeddel, D. V. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495–504.

    Article  PubMed  CAS  Google Scholar 

  65. Malinin, N. L., Boldin, M. P., Kovalenko, A. V., and Wallach, D. (1997) MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 385 (6616), 540–544.

    Article  PubMed  CAS  Google Scholar 

  66. Beg, A. A. and Baldwin, A. S. (1996) An essential role for NF-KB in preventing TNF-ainduced cell death. Science 274, 782–784.

    Article  PubMed  CAS  Google Scholar 

  67. Cosman, D. (1994) A family of ligands for the TNF receptor superfamily. Stem Cells 12, 440–455.

    Article  PubMed  CAS  Google Scholar 

  68. Nagata, S. (1994) Apoptosis regulated by a death factor and its receptor: Fas ligand and Fas. Phil. Trans. Royal Soc. Lond. B 345, 281–287.

    Article  CAS  Google Scholar 

  69. Nagata, S. and Golstein, P. (1995) The Fas death factor. Science 267, 1449–1462.

    Article  PubMed  CAS  Google Scholar 

  70. Matiba, B., Marian, S. M., and Krammer, P. H. (1997) The CD95 system and the death of a lymphocyte. Semin. Immunol. 9, 59–68.

    Article  PubMed  CAS  Google Scholar 

  71. Wong, B., Park, C. G., and Choi, Y. (1997) Identifying the molecular control of T-cell death; on the hunt for killer genes. Semin. Immunol. 9, 7–16.

    Article  PubMed  CAS  Google Scholar 

  72. Chinnaiyan, A. M., O’Rourke, K., Yu, G.-L., Lyons, R. H., Garg, M., Duan, D. R., Xing, L., Genii, R., Ni. J., and Dixit, V. M. (1996) Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science 274, 990–992.

    CAS  Google Scholar 

  73. Pan, G., O’Rourke, K., Chinnaiyan, A. M., Gentz, R., Ebner, R., Ni, J., and Dixit, V. M. (1997) The receptor for the cytotoxic ligand TRAIL. Science 276, 111–113.

    Article  PubMed  CAS  Google Scholar 

  74. Brojatsch, J., Naughton, L., Rolls, M. M., Zingler, K., and Young, J. A. T. (1996) CARI, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis. Cell 87, 845–855.

    Article  PubMed  CAS  Google Scholar 

  75. Singer, N. G., Robert, F. D., and Fox, D. A. (1994) Structure on the cell surface: update from the fifth international workshop on human leukocyte differentiation antigen. Arthritis Rheum 37, 1245–1248.

    CAS  Google Scholar 

  76. Rouvier, E., Luciani, M. F. and Golstein, P. (1993) Fas involvement in Cat+-dependent T cell-mediated cytotoxicity. J. Exp. Med. 177, 195–200.

    Article  PubMed  CAS  Google Scholar 

  77. Lowin, B., Hahne, M., Mattmann, C., Tschopp, J. (1994) Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370, 650–652.

    Article  PubMed  CAS  Google Scholar 

  78. Cheng, J., Liu, C., Koopman, W. J., and Mountz, J. D. (1995) Characterization of human Fas gene: exon/intron organization and promoter region. J. Immunol. 154, 1239–1245.

    PubMed  CAS  Google Scholar 

  79. Cheng, J., Zhou, T., Liu, C., Shapiro, J. P., Brauer, M. J., Kiefer, M. C., Barr, P. J., and Mountz, J. D. (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263, 1759.

    Article  PubMed  CAS  Google Scholar 

  80. Liu, C., Cheng, J., and Mountz, J. D. (1995) Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation. Biochem. J. 310, 957–963.

    PubMed  CAS  Google Scholar 

  81. Tokano, Y., Miyake, S., Kayagaki, N., Nozawa, K., Morimoto, S., Azuma, M., Yagita, H., Takasaki, Y., Okumura, K., and Hashimoto, H. (1996) Soluble Fas molecule in the serum of patients with systemic lupus erythematosus. J. Clin. Immunol. 16, 261–265.

    Article  PubMed  CAS  Google Scholar 

  82. Hasunuma, T., Kayagaki, N., Asahara, H., Motokawa, S., Kobata, T., Yagita, H., Aono, H., Sumida, T., Okumura, K., and Nishioka, K. (1997) Accumulation of soluble Fas in inflamed joints of patients with rheumatoid arthritis. Arthritis Rheum. 40, 80–86.

    Article  PubMed  CAS  Google Scholar 

  83. Okubo, M., Ishida, H., and Kasukawa, R. (1996) Elevated levels of soluble Fas in systemic lupus erythematosus: comment in the article by Knipping, et al. Arthritis Rheum. 39, 1612–1614.

    Article  PubMed  CAS  Google Scholar 

  84. Jodo, S., Kobayashi, S., Kayagaki, N., Ogura, N., Feng, Y., Amasaki, Y., Fujisaku, A., Azuma, M., Yagita, H., Okumura, K., and Koike, T. (1997) Serum levels of soluble Fas/APO-1 (CD95) and its molecular structure in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. Clin. Exp. Immunol. 107, 89–95.

    Article  PubMed  CAS  Google Scholar 

  85. Fadeel, B., Samuelsson, A., Hachiya, T., et al. (1996) Elevated serum levels of soluble Fas/APO-1 in human immunodeficiency virus-infected individuals. Blood 88, 4727–4730.

    PubMed  CAS  Google Scholar 

  86. Midis, G. P., Shen, Y., and Owen-Schaub, L. B. (1996) Elevated soluble Fas (sFas) levels in non-hematopoietic human malignancy. Cancer Res. 56, 3870–3874.

    PubMed  CAS  Google Scholar 

  87. Yano, H., Fukuda, K., Haramaki, M., et al. (1996) Expression of Fas and anti-Fas-mediated apoptosis in human hepatocellular carcinoma cell lines. J. Hepatol. 25, 454–464.

    Article  PubMed  CAS  Google Scholar 

  88. Natoli, G., Ianni, A., Costanzo, A., et al. (1995) Resistance to Fas-mediated apoptosis in human hepatoma cells. Oncogene 11, 1157–1164.

    PubMed  CAS  Google Scholar 

  89. Goel, N., Ulrich, D. T., St. Clair, E. W., Fleming, J. A., Lynch, D. H., and Seldin, M. F. (1995) Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease. Arthritis Rheum. 38, 1738–1743.

    Article  PubMed  CAS  Google Scholar 

  90. Knipping, E., Krammer, P. H., Onel, K. B., Lehman, T. J., Mysler, E., and Elkon, K. B. (1995) Levels of soluble Fas/APO-1/CD95 in systemic lupus erythematosus and juvenile rheumatoid arthritis. Arthritis Rheum. 38, 1735–1737.

    Article  PubMed  CAS  Google Scholar 

  91. Shortman, K. and Scollay, R. (1994) Death in the thymus. Nature 372, 44–45.

    Article  PubMed  CAS  Google Scholar 

  92. Ritter, M. and Crispe, I. N. (1992) Structure and development, in The Thymus. (Male, D., ed.), Oxford University Press, New York, pp. 9–25.

    Google Scholar 

  93. Singer, G. G., Carrera, A. C., Marshak-Rothstein, A., Martínez, C., and Abbas, A. K. (1994) Apoptosis, Fas and systemic autoimmunity: the MRL-1pr/lpr model. Curr. Opin. Immunol. 6, 913–920.

    Article  PubMed  CAS  Google Scholar 

  94. Watanabe, D., Suda, T., Hashimoto, H., and Nagata, S. (1995) Constitutive activation of the Fas ligand gene in mouse lymphoproliferative disorders. EMBO J. 14, 12–18.

    PubMed  CAS  Google Scholar 

  95. Kotzin, B. L., Babcock, S. K., and Herron, L. R. (1988) Deletion of potentially self-reactive T cell receptor specificities in L3T4-, Lyt2- T cells of 1pr mice. J. Exp. Med. 168, 2221–2229.

    Article  PubMed  CAS  Google Scholar 

  96. Singer, P. A., Balderas, R. S., McEvilly, R. J., Bobardt, M., and Theofilopoulos, A. N. (1989) Tolerance-related V(clonal deletions in normal CD4–CD8-, TCR-ar and abnormal 1pr and gld cell populations. J. Exp. Med. 170, 1869–1877.

    Article  PubMed  CAS  Google Scholar 

  97. Mountz, J. D., Smith, T. M., and Toth, K. S. (1990) Altered expression of self-reactive T cell receptor Vß regions in autoimmune mice. J. Immunol. 144, 2159–2166.

    PubMed  CAS  Google Scholar 

  98. Zhou, T., Bluethmann, H., Eldridge, J., Berry, K., and Mountz, J. D. (1991) Abnormal thymocyte development and production of autoreactive T cells in TCR transgenic autoimmune mice. J. Immunol. 147, 466–474.

    PubMed  CAS  Google Scholar 

  99. Herron, L. R., Eisenberg, R. A., Roper, E., et al. (1993) Selection of the T cell receptor repertoire in 1pr mice. J. Immunol. 151, 3450–3459.

    PubMed  CAS  Google Scholar 

  100. Mountz, J. D., Bluethmann, H., Zhou, T., and Wu, J. (1994) Defective clonal deletion and anergy induction in TCR transgenic 1pr/lpr mice. Semin. Immunol. 6, 27–37.

    Article  PubMed  CAS  Google Scholar 

  101. Castro, J. E., Listman, J. A., Jacobson, B. A., Wang, Y., Lopez, P. A., Ju, S., Finn, P. W., and Perkins, D. L. (1996) Fas modulation of apoptosis during negative selection of thymocytes. Immunity 5, 617–627.

    Article  PubMed  CAS  Google Scholar 

  102. Zhou, T., Bluethmann, H., Eldridge, J., Berry, K., and Mountz, J. M. (1993) Origin of CD4CD8- B220+ T cells in MRL-1pr/lpr mice. J. Immunol. 150, 3651–3667.

    PubMed  CAS  Google Scholar 

  103. Sidman, C. L., Marshall, J. D., and von Boehmer, H. (1992) Transgenic T cell receptor interactions in the lymphoproliferative disease and autoimmune syndromes of 1pr and gld mutant mice. Eur. J. Immunol. 22, 499–504.

    Article  PubMed  CAS  Google Scholar 

  104. Kabelitz, D., Pohl, T., and Pechhold, K. (1993) Activation-induced cell death (apoptosis) of mature peripheral T lymphocytes. Immunol. Today 14, 338–339.

    Article  PubMed  CAS  Google Scholar 

  105. Trauth, B. C., Klas, C., Peters, A. M., et al. (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245, 301–305.

    Article  PubMed  CAS  Google Scholar 

  106. Klas, C., Debatin, K. M., Jonker, R. R., et al. (1993) Activation interferes with the APO-1 pathway in mature human T cells. Int. Immunol. 5, 625–630.

    Article  PubMed  CAS  Google Scholar 

  107. Bossu, P., Singer, G. G., Andres, P., Ettinger, R., Marshak-Rothstein, A., and Abbas, A. K. (1993) Mature CD4+ T lymphocytes from MRL-lpr mice are resistant to receptor-mediated tolerance and apoptosis. J. Immunol. 151, 7233–7239.

    PubMed  CAS  Google Scholar 

  108. Van Parijs, L., Ibraghimov, A., and Abbas, A. K. (1996) The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 4, 321–328.

    Article  PubMed  Google Scholar 

  109. Ju, S. T., Panka, D. J., Cui, H., Ettinger, R., el-Khatib, M., Sherr, D. H., Stanger, B. Z., Marshak-Rothstein, A. (1995) Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373, 444–448.

    Article  PubMed  CAS  Google Scholar 

  110. Alderson, M. R., Tough, T. W., Davis-Smith, T., Braddy, S., Falk, B., Schooley, K. A., Goodwin, R. G., Smith, C. A., Ramsdell, F., and Lynch, D. H. (1995) Fas ligand mediates activation-induced cell death in human T lymphocytes. J. Exp. Med. 181, 71–77.

    Google Scholar 

  111. Dhein, J., Walczak, H., Baumler, C., Debatin, K. M., and Krammer, P. H. (1995) Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 373, 438–441.

    Article  PubMed  CAS  Google Scholar 

  112. Brunner, T., Mogil, R. J., LaFace, D., Yoo, N. J., Manboubl, A., Echeverre, F., Martin, J., Force, W. R., Lynch, D. H., Ware, C. F., and Green, D. R. (1995) Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373, 441–444.

    Article  PubMed  CAS  Google Scholar 

  113. Green, D. R. and Scott, D. W. (1994) Activation-induced apoptosis in lymphocytes. Curr. Opin. Immunol. 6, 476–483.

    Article  PubMed  CAS  Google Scholar 

  114. Tucek-Szabo, C. L., Andjelic, S., Lacy, E., Elkon, K. B., and Nikolic-Zugic, J. (1996) Surface T cell Fas receptor/CD95 regulation, in vivo activation, and apoptosis: activation-induced death can occur without Fas receptor. J. Immunol. 156, 192–200.

    PubMed  CAS  Google Scholar 

  115. Russell, J. H. (1995) Activation-induced death of mature T cells in the regulation of immune responses. Curr. Opin. Immunol. 7, 382–388.

    Article  PubMed  CAS  Google Scholar 

  116. Dhein, J., Walczak, H., Baumler, C., Debatin, K. M., and Krammer, P. H. (1995) Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 373, 438–441.

    Article  PubMed  CAS  Google Scholar 

  117. Rathmell, J. C., Cooke, M. P., Ho, W. Y., Grein, J., Townsend, S. E., Davis, M. M., and Goodnow, C. C. (1995) CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. Nature 376, 181–184.

    Article  PubMed  CAS  Google Scholar 

  118. Scott, D. W., Grdina, T., and Shi, Y. (1996) T cells commit suicide, but B cells are murdered. J. Immunol. 156, 2352–2356.

    PubMed  CAS  Google Scholar 

  119. Hargreaves, R. G., Borthwick, N. J., Montani, M. S., Piccolella, E., Carmichael, P., Lechler, R. I., Akbar, A. N., and Lombardi, G. (1997) Dissociation of T cell anergy from apoptosis by blockade of Fas/Apo-1 (CD95) signaling. J. Immunol. 158, 3099–3107.

    PubMed  CAS  Google Scholar 

  120. Zhang, L. (1996) The fate of adoptively transferred antigen-specific T cells in vivo. Eur. J. Immunol. 26, 2208–2214.

    Article  PubMed  CAS  Google Scholar 

  121. Palmiter, R. D. and Brinster, R. L. (1986) Germ-line transformation of mice. Annu. Rev. Genetics 20, 465–499.

    Article  CAS  Google Scholar 

  122. Mountz, J. D., Zhou, T., and Johnson, L. (1990) Production of transgenic mice and application to immunology and autoimmunity. Am. J. Med. Sci. 300, 322–329.

    Article  PubMed  CAS  Google Scholar 

  123. Wu, J., Zhou, T., Zhang, J., He, J., Guise, W. C., Mountz, J. D. (1994) Correction of accelerated autoimmune disease by early replacement of the mutated 1pr gene with the normal Fas apoptosis gene in the T cells of transgenic MRL-1pr/lpr mice. Proc. Natl. Acad. Sci. USA 91, 2344–2348.

    Google Scholar 

  124. Greaves, D. R., Wilson, F. D., Lang, G., and Kioussis, D. (1989) Human CD2 3’-flanking sequences confer high-level, T cell-specific, position-independent gene expression in trans-genic mice. Cell 56, 979–986.

    Article  PubMed  CAS  Google Scholar 

  125. Street, R. E. and Mossman, T. R. (1991) Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 5, 171–177.

    PubMed  CAS  Google Scholar 

  126. Zhou, T., Edwards, C. K. III, and Mountz, J. D. (1995) Prevention of age-related T cell apoptosis defect in CD2-fas transgenic mice. J. Exp. Med. 182, 129–137.

    Article  PubMed  CAS  Google Scholar 

  127. Moreland, L. W., Sewell, K. L., Trentham, D. E., Bucy, R. P., Sullivan, W. F., Schrohenloher, R. E., Schmerling, R. H., Parker, K. C., Swartz, W. G., Woodworth, T. G., and Koop-man, W. J. (1995) Diphtheria interleukin-2 fusion protein (DAB486IL-2) in refractory rheumatoid arthritis: a double-blind placebo-controlled trial with open label extension. Arthritis Rheum. 38, 1177–1186.

    Article  PubMed  CAS  Google Scholar 

  128. Arend, W. P. and Dayer, J. M. (1995) Inhibition of the production and effects of interleukin1 and tumor necrosis factor in rheumatoid arthritis. Arthritis Rheum. 38, 151–160.

    Article  PubMed  CAS  Google Scholar 

  129. Salmons, B. and Gunzburg, W. H. (1993) Targeting of retroviral vectors for gene therapy. Hum. Gene Ther. 4, 129–141.

    Article  PubMed  CAS  Google Scholar 

  130. Harris, C. E., Agarwal, S., Hu, P., Wagner, E., and Curiel, D. T. (1993) Receptor-mediated gene transfer to airway epithelial cells in primary culture. Am. J. Resp. Cell Mol. Biol. 9, 441–447.

    Article  CAS  Google Scholar 

  131. Deshane, J., Cabrera, G., Grim, J. E., Siegal, G. P., Pike, J., Alvarez, R. D., and Curiel, D. T. (1995) Targeted eradication of ovarian cancer mediated by intracellular expression of antierbB-2 single-chain antibody Gynecol. Oncol. 59, 8–14.

    Article  PubMed  CAS  Google Scholar 

  132. Michael, S. I., Huang, C. H., Romer, M. U., Wagner, E., Hu, P. C., and Curiel, D. T. (1993) Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway. J. Biol. Chem. 268, 6866–6869.

    PubMed  CAS  Google Scholar 

  133. Gao, L., Wagner, E., Cotton, M., Agarwal, S., Harris, C., Romer, M., Miller, L., Hu, P. C., and Curiel, D. (1993) Direct in vivo gene transfer to airway epithelium employing adenovirus-polylysine-DNA complexes. Hum. Gene Ther. 4, 17–24.

    Article  PubMed  Google Scholar 

  134. Curiel, D. T. (1993) Adenovirus facilitation of molecular conjugate-mediated gene transfer. Prog. Med. Virol. 40, 1–18.

    Article  PubMed  CAS  Google Scholar 

  135. Schwarzenberger, P., Spence, S. E., Gooya, J. M., Michiel, D., Curiel, D. T., Ruscetti, F. W., and Keller, J. R. (1996) Targeted gene transfer to human hematopoietic progenitor cell lines through the c-kit receptor. Blood 87, 472–478.

    PubMed  CAS  Google Scholar 

  136. Michael, S. I., Hong, J. S., Curiel, D. T., and Engler, J. A. (1995) Addition of a short peptide ligand to the adenovirus fiber protein. Gene Ther. 2, 660–668.

    PubMed  CAS  Google Scholar 

  137. Garver, R. I. Jr., Goldsmith, K. T., Rodu, B., Hu, P. C., Sorscher, E. J., and Curiel, D. T. (1994) Strategy for achieving selective killing of carcinomas. Gene Ther. 1, 46–50.

    PubMed  CAS  Google Scholar 

  138. Wu, K., Yuan, J., and Lasky, L. A. (1996) Characterization of a novel member of the macrophage mannose receptor type C lectin family. J. Biol. Chem. 271, 21323–21330.

    Article  PubMed  CAS  Google Scholar 

  139. Jiang, W., Swiggard, W. J., Heufler, C., Peng, M., Mirza, A., Steinman, R. M., and Nussenzweig, M. C. (1995) The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375, 151–155.

    Article  PubMed  CAS  Google Scholar 

  140. Clarke, S., Greaves, D. R., Chung, L. P., Tree, P., and Gordon, S. (1996) The human lysozyme promoter directs reporter gene expression to activated myelomonocytic cells in transgenic mice. Proc. Natl. Acad. Sci. USA 93, 1434–1438.

    Article  PubMed  CAS  Google Scholar 

  141. Ebbinghaus, S. W., Vigneswaran, N., Miller, C. R., Chee-Awai, R. A., Mayfield, C. A., Curiel, D. T., and Miller, D. M. (1996) Efficient delivery of triplex forming oligonucleotides to tumor cells by adenovirus-polylysine complexes. Gene Ther. 3, 287–297.

    PubMed  CAS  Google Scholar 

  142. Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., and Ferguson, T. A. (1995) Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270, 1189–1192.

    Article  PubMed  CAS  Google Scholar 

  143. Lau, H. T., Yu, M., Fontana, A., and Stoeckert, C. J. Jr. (1996) Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 273, 109–112.

    Article  PubMed  CAS  Google Scholar 

  144. Allison, J., Georgiou, H. M., Strasser, A., and Vaux, D. L. (1997) Transgenic expression of CD95 ligand on islet 13 cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc. Natl. Acad. Sci. USA 94, 3943–3947.

    Article  PubMed  CAS  Google Scholar 

  145. Choulika, A., Guyot, V., and Nicolas, J. F. (1996) Transfer of single gene-containing long terminal repeats into the genome of mammalian cells by a retroviral vector carrying the cre gene and the loxP site. J. Virol. 70, 1792–1798.

    PubMed  CAS  Google Scholar 

  146. Zhang, H.-G., Bibao, G., Zhou, T., Contreas, J. L., Gomez-Navarro, J., Feng, M., Saito, I., Mountz, J. D., and Curiel, D. T. (1998) Application of a Fas ligand encoding a recombinant adenovirus vector for prolongation of transgene expression. J. Virol. 72, 2483–2490.

    PubMed  CAS  Google Scholar 

  147. Zhang, H.-G., Liu, D., Yang, P. A., Wang, Z., Curiel, D. T., Zhou, T., and Mountz, J. D. (1998) Induction of specific T-cell tolerance by adenovirus-infected Fas ligand expressing antigen presenting cells. Nature Biotechnol. 16, 1045–1049.

    Article  CAS  Google Scholar 

  148. Shultz, L. D., Schweitzer, P. A., Rajan, T. V., Yi, T., Ihle, J. N., Matthews, R. J., Thomas, M. L., and Beier, D. R. (1993) Mutations at the murine motheaten locus are within the hematopoietic cell protein tyrosine phosphatase (HCP) gene. Cell 73, 1445–1454.

    Article  PubMed  CAS  Google Scholar 

  149. Su, X., Zhou, T., Wang, Z., Yang, P., Jope, R. S., and Mountz, J. D. (1995) Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis. Immunity 2, 353–362.

    Article  PubMed  CAS  Google Scholar 

  150. Hsu, H.-C., Zhou, T., Yang, P. A., Herrera, G. A., and Mountz, J. D. (1997) Increased acute-phase response and renal amyloidosis of aged CD2-fas transgenic mice. J. Immunol. 158, 5988–5996.

    PubMed  CAS  Google Scholar 

  151. Cheng, J., Liu, C., Yang, P., Zhou, T., and Mountz, J. D. (1997) Increased lymphocyte apoptosis in Fas ligand transgenic mice. J. Immunol. 159, 674–684.

    PubMed  CAS  Google Scholar 

  152. Mountz, J. D., Zhou, T., Eldridge, J., Berry, K., and Bluthmann, H. (1990) Transgenic rearranged T cell receptor gene inhibits lymphadenopathy and accumulation of CD4–CD8B220+ T cells in 1pr/lpr mice. J. Exp. Med. 172, 1805–1817.

    Article  PubMed  CAS  Google Scholar 

  153. Zhou, T., Cheng, J., Yang, P., Wang, Z., Liu, C., Su, X., Bluethmann, H., and Mountz, J. D. (1996) Inhibition of Nurrl/Nur77 leads to inefficient clonal deletion of self-reactive T cells. J. Exp. Med. 183, 1879–1892.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Hui-Chen Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huang-Ge Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John D. Mountz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Section on Rheumatology, Department of Internal Medicine, The Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Gary M. Kammer MD

  2. Division of Rheumatology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, USA

    George C. Tsokos MD

  3. Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC, USA

    George C. Tsokos MD

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hsu, HC., Zhang, HG., Zhou, T., Mountz, J.D. (1999). Management of Murine Lupus by Correction of Fas and Fas Ligand-Induced Apoptosis. In: Kammer, G.M., Tsokos, G.C. (eds) Lupus. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-703-1_40

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-703-1_40

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5686-9

  • Online ISBN: 978-1-59259-703-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation