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Inhibition of the alloantibody response by CD95 ligand

Nature Medicine volume 3, pages 843–848 (1997)Cite this article

Abstract

We investigated the effect of Fas/APO1-ligand (CD95L) gene transfer on allogeneic immune responses in vivo. A colon carcinoma cell line from BALB/c mice, CT26, was stably transfected with a vector encoding mouse CD95L and was inoculated into C57BL/6 mice. CD95L expression markedly reduced allogeneic cytotoxic T lymphocyte and helper T lymphocyte activity directed toward CT26. Strikingly, expression of CD95L on these allogeneic tumors completely inhibited the generation of alloantibodies of both IgM and IgG subclasses. Thus, CD95L inhibited alloantibody production and conferred localized immune suppression through this mechanism. These results provide insight into the role of CD95L in regulating the alloantibody response and the generation of local immune responses.

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References

  1. Matzinger, P. & Bevan, M.J. Why do so many lymphocytes respond to major histocompatibility antigens? Cell. Immunol. 29, 1–5 (1977).

    Article  CAS  Google Scholar 

  2. Sayegh, M.H., Watschinger, B. & Carpenter, C.B. Mechanisms of T cell recognition of alloantigen: The role of peptides. Transplantation 57, 1295–1302 (1994).

    Article  CAS  Google Scholar 

  3. Bradley, J.A., Mowat, A.M. & Bolton, E.M. Processed MHC class I alloantigen as the stimulus for CD4+ T-cell dependent antibody-mediated graft rejection. Immunol. Today 13, 434–438 (1992).

    Article  CAS  Google Scholar 

  4. Bishop, D.K., DeBruyne, L.A., Chan, S., Xu, S. & Eichwald, E.J. Dissociation of mouse cardiac transplant rejection and donor alloantigen-specific T cell responsive-ness. Transplant. Immunol. 3, 222–228 (1995).

    Article  CAS  Google Scholar 

  5. Itoh, N. et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233–243 (1991).

    Article  CAS  Google Scholar 

  6. 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 75, 1169–1178 (1993).

    Article  CAS  Google Scholar 

  7. Nagata, S. & Golstein, P. The Fas death factor. Science 267, 1449–1456 (1995).

    Article  CAS  Google Scholar 

  8. Lynch, D.H., Ramsdell, F. & Alderson, M.R. Fas and FasL in the homeostatic regulation of immune responses. Immunol. Today 16, 569–574 (1995).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Chan, S.Y., DeBruyne, L.A., Goodman, R.E., Eichwald, E.J. & Bishop, D.K. In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection, Transplantation 59, 1155–1161 (1995).

    Article  CAS  Google Scholar 

  11. Brunner, T. et al. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373, 441–444 (1995).

    Article  CAS  Google Scholar 

  12. Ju, S. et al. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373, 444–448 (1995).

    Article  CAS  Google Scholar 

  13. Zheng, L. et al. Induction of apoptosis in mature T cells by tumor necrosis factor. Nature 377, 348–351 (1995).

    Article  CAS  Google Scholar 

  14. Kupfer, A. & Singer, S. Cell biology of cytotoxic and helper T cell functions. Annu. Rev. Immunol. 7, 309 (1989).

    Article  CAS  Google Scholar 

  15. Harriman, W., Volk, H., Defranoux, N. & Wabl, M. Immunoglobulin class switch recombination. Annu. Rev. Immunol. 11, 361–384 (1993).

    Article  CAS  Google Scholar 

  16. Rouvier, E., Luciani, M.F. & Gelstein, P. Fas involvement in Ca2+-independentT cell-mediated cytotoxicity. J. Exp. Med. 177, 195 (1993).

  17. Garrone, P. et al. Fas ligation induces apoptosis of CD40-activated human B lymphocytes. J. Exp. Med. 182, 1265–1273 (1995).

    Article  CAS  Google Scholar 

  18. Schattner, E. et al. CD40 ligation induces APO-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway. J. Exp. Med. 182, 1557–1565 (1995).

    Article  CAS  Google Scholar 

  19. Cleary, A.M., Fortune, S.M., Yellin, M.J., Chess, L. & Lederman, S. Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J. Immunol. 155, 3329–3337 (1995).

    CAS  PubMed  Google Scholar 

  20. Daniel, P.T. & Krammer, P.M. Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J. Immunol. 152, 5624–5632 (1994).

    CAS  PubMed  Google Scholar 

  21. Rothstein, T.L. et al. Protection again Fas-dependent Thl-mediated apoptosis by antigen receptor engagement in B cells. Nature 374, 163–165 (1995).

    Article  CAS  Google Scholar 

  22. Rathmell, J.C., Townsend, S.E., Xu, J.C., Flavell, R.A. & Goodnow, C.C. Expansion or elimination of B cells in vivo: Dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Cell 87, 319–329 (1996).

    Article  CAS  Google Scholar 

  23. Bishop, D.K. et al. Helper T lymphocyte unresponsiveness to cardiac allografts following transient depletion of CD4-positive cells. Transplantation 58, 576–584 (1994).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Bellgrau, D. et al. A role for CD95 ligand in preventing graft rejection. Nature 377, 630–632 (1995).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Yagita, H., Seino, K., Kayagaki, N. & Okumura, K. CD95 ligand in graft rejection. Nature 379, 682–683 (1996).

    Article  CAS  Google Scholar 

  28. Plautz, G.E. et al. Immunotherapy of malignancy by in vivo gene transfer into tumors. Proc. Natl. Acad. Sci. USA 90, 4645–4649 (1993).

    Article  CAS  Google Scholar 

  29. Ellison, J.W., Berson, B.J. & Hood, L.E. The nucleotide sequence of a human immunoglobulin C gamma 1 gene. Nucleic. Acids. Res. 10, 4071–4079 (1982).

    Article  CAS  Google Scholar 

  30. Orosz, C.G., Horstemeyer, B., Zinn, N.E. & Bishop, D.K. Development and evaluation of an IDA technique that can discriminate in vivo alloactivated CTL from their naive CTL precursors. Transplantation 47, 189–194 (1989).

    Article  CAS  Google Scholar 

  31. Bishop, D.K. & Orosz, C. Limiting dilution analysis for alloreactive TCGF secretory T cells. Transplantation 47, 671–677 (1989).

    Article  CAS  Google Scholar 

  32. Schroder, J.M., Mrowietz, U., Morita, E. & Christophers, E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J. Immunol. 139, 3474–3483 (1987).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, 1150 West Medical Center Drive, 4520 MSRB I, Ann Arbor, Michigan, 48109-0650, USA

    Hiroshi Arai & Gary J. Nabel

  2. Department of Surgery, Section of General Surgery, 1150 West Medical Center Drive, A560 MSRB II, Ann Arbor, Michigan, 48109-0654, USA

    Sherri Y. Chanz & D. Keith Bishop

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  1. Hiroshi Arai
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  2. Sherri Y. Chanz
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  3. D. Keith Bishop
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  4. Gary J. Nabel
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Arai, H., Chanz, S., Bishop, D. et al. Inhibition of the alloantibody response by CD95 ligand. Nat Med 3, 843–848 (1997). https://doi.org/10.1038/nm0897-843

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