The use of tolerance for transplantation across xenogeneic barriers

Abstract

The success of human organ transplantation as a clinical treatment has created a conundrum for the transplant community. It has caused a shortage of human donor organs and uncovered problems of chronic immunosuppression in those lucky enough to receive organ transplants due to their use of chronic immunosuppressive drugs. Our aim is to attempt to approach both issues by establishing specific transplantation tolerance to pig organ grafts.

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References

  1. 1

    Billingham, R.E., Brent, L. and Medawar, R.B. 1953. Actively acquired tolerance to foreign cells. Nature 172: 603–606.

  2. 2

    Ho, M. and Dummer, J.S. 1990. Risk factors and approaches to infections in transplant recipients. pp. 2284–2291 in Principles and Practice of Infectious Diseases, 2nd ed. Mandell, G.C., Douglas, G.R. Jr., and Bennet, J.E. (eds.). Churchill Livingstone, New York.

  3. 3

    Fishman, J.A. 1994. Miniature swine as organ donors for man: Strategies for prevention of xenotransplant-associated infections. Xenotransplantation 1: 47–57.

  4. 4

    Michaels, M.G. and Simmons, R.L.,1994. Xenotransplant-Associated Zoonoses. Transplantation 57: 1–7.

  5. 5

    Sachs, D.H., Leight, G., Cone, J., Schwarz, S., Stuart, L. and Rosenberg, S. 1976. Transplantation in miniature swine. I. Fixation of the major histocompatibility complex. Transplantation 22: 559–567.

  6. 6

    Sachs, D.H. 1992. MHC Homozygous Miniature Swine pp. 3–15 in Swine as Models in Biomedical Research. Swindle, M.M., Moody, D.C., and Phillips, L.D. (eds.). Iowa State University Press, Ames, Iowa.

  7. 7

    Sachs, D.H. 1994. The pig as a potential xenograft donor. Vet. Immunol. Immunopathol. 43: 185–191.

  8. 8

    Calne, R.Y. 1970. Organ transplantation between widely disparate species. Transplant Proc. 2: 550–556.

  9. 9

    Platt, J.L., Fischel, R.J., Matas, A.J., Reif, S.A., Bolman, R.M. and Bach, F.H. 1991. Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. Transplantation 52: 214–220.

  10. 10

    Sandrin, M.S., Vaughan, H.A., Dabkowski, P.L. and McKenzie, I.F.C., 1993. IgM antibodies in human serum react predominantly with gal α(1,3) gal epitopes. Proc. Natl. Acad. Sci. USA 90: 11391–11395.

  11. 11

    Parker, W.R., Bruno, D., Holzknecht, Z.E. and Platt, J.L. 1994. Xenoreactive natural antibodies: Isolation and initial characterization. J. Immuno. 153: 3791–3803.

  12. 12

    Good, A.H., Cooper, D.K.C., Malcolm, A.J., Ippolito, R.M., Koren, E., Neethling, F.A., Ye, Y., Zuhdi, N. and Lamontagne, L.R. 1992. Identification of carbohydrate structures that bind human anti-porcine antibodies: Implications for discordant xenografting in humans. Transplant Proc. 24: 559–562.

  13. 13

    Galili, U. and Swanson, K. 1991. Gene sequences suggest inactivation of α1,3-galactosyltransferase in catarrhines after the divergence of apes from monkeys. Proc. Natl. Acad. Sci. USA 88: 7401–7404.

  14. 14

    Galili, U., Shohet, S.B., Kobrin, E., Stults, C.L.M. and Macher, B.A., 1988. Man, apes, and old world monkeys differ from other mammals in the expression of α-galactosyl epitopes on nucleated cells. J. Biol. Chem. 263: 17755–17762.

  15. 15

    Alexandre, G.R., Squifflet, J.R., De Bruyere, M., Latinne, D., Reding, R., Gianello, P., Carlier, M. and Pirson, Y. 1987. Present experiences in a series of 26 ABO-incompatible living donor renal allografts. Transplant Proc. 19: 4538–4542.

  16. 16

    Alexandre, G.P.J., Gianello, P., Latinne, D. et al. 1989. Plasmapheresis and splenectomy in experimental renal Xenotransplantation. pp. 259–266 in Xenograft 25. Hardy, M.A. (ed.). Excerpta Medica, New York.

  17. 17

    Cooper, D.K.C. 1992. Depletion of natural antibodies in non-human primates—A step towards successful discordant xenografting in humans. Clin. Transpl. 6: 178–183.

  18. 18

    Sablinski, T., Latinne, D., Gianello, P., Bailin, M., Bergen, K. and Colvin, R.B. 1995. Xenotransplantation of pig kidneys to nonhuman primates: I. Development of the model. Xenotransplantation 2: 264–270.

  19. 19

    Sachs, D.H. and Sablinski, T. 1995. Tolerance across discordant xenogeneic barriers. Xenotransplantation 2: 234–239.

  20. 20

    Oriol, R., Ye, Y., Koren, E. and Cooper, D.K. 1993. Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for hyperacute vascular rejection in pig-to-man organ Xenotransplantation. Transplantation 56: 1433–1442.

  21. 21

    Leventhal, J.R., Dalmasso, A.P., Cromwell, J.W., Platt, J.L., Manivel, C.J., Bolman, R.M. and Matas, A.J. 1993. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation 55: 857–866.

  22. 22

    Pruitt, S.K., Kirk, A.D., Bollinger, R.R., Marsh, H.C., Jr Collins, B.H., Levin, J.L. et al. 1994. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation 57: 363–370.

  23. 23

    Kobayashi, T., Taniguchi, S., Ye, Y., Niekrasz, M., Kosanke, S., Neethling, F.A. et al. 1996. Delayed xenograft rejection in 03-depleted discordant (pig-to-baboon) cardiac xenografts treated with cobra venom factor. Transplant Proc. 28: 560.

  24. 24

    Langford, G.A., Yannoutsos, N., Cozzi, E., Lancaster, R., Elsome, K., Chen, R. et al. 1994. Production of pigs transgenic for human decay accelerating factor. Transplant Proc. 26: 1400–1401.

  25. 25

    Fodor, W.L., Williams, B.L., Matis, L.A., Madri, J.A., Rollins, S.A., Knight, J.W. et al. 1994. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc. Natl. Acad. Sci. USA 91: 11153–11157.

  26. 26

    Loveland, B.E., Johnstone, R.W., Russell, S.M., Thorley, B.R. and McKenzie, I.F. 1993. Different membrane cofactor protein (CD46) isoforms protect transfected cells against antibody and complement mediated lysis. Transpl. Immunol. 1: 101–108.

  27. 27

    McCurry, K.R., Kooyman, D.L., Alvarado, C.G., Cotterell, A.H., Martin, M.J., Logan, J.S. and Platt, J.L. 1995. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nat. Med. 1: 423–427.

  28. 28

    Cozzi, E. and White, D.J.G. 1995. The generation of transgenic pigs as potential organ donors for humans. Nature Medicine 1: 964–966.

  29. 29

    White, D.J. 1996. HDAF transgenic pig organs: are they concordant for human transplantation? Xeno. 4: 50–54.

  30. 30

    Sandrin, M.S., Fodor, W.L., Mouhtouris, E., Osman, N., Cohney, S., Rollins, S.A. et al. 1995. Enzymatic remodelling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nat Med. 1: 1261–1267.

  31. 31

    Sharma, A., Okabe, J.F., Birch, P., Platt, J.L. and Logan, J.S. 1996. Reduction in the level of gal α(1,3) gal in transgenic mice and pigs by the expression of an α(1,2) fucosyltransferase. Proc. Natl. Acad. Sci. USA 93: 7190–7195.

  32. 32

    Blakely, M.L., Van der Werf, M.L., Blakely, W.J., Berndt, M.C., Dalmasso, A.P., Bach, M.L., Blakely, F.H., and Hancock, W.W., 1994. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 58: 1059–1066.

  33. 33

    Leventhal, J.R., Matas, A.J., Sun, L.H., Reif, S., Bolman, R.M.III, Dalmasso, A.R., and Platt, J.L . 1993. The immunopathology of cardiac xenograft rejection in the guinea pig to rat model. Transplantation 56: 1–8.

  34. 34

    Platt, J.L., 1996. Recent progress and current perspectives. Current Opinion in Immunology 8: 721–728.

  35. 35

    Bach, F.H., Winkler, H., Ferran, C., Hancock, W.W. and Robson, B.C. 1996. Delayed xenograft rejection. Immunology Today 17: 379–384.

  36. 36

    Richards, A.C., Tucker, A.W., Carrington, C.A., White, D.J.G. and Wallwork, J. 1996. Neutrophils and Xenotransplantation. Lancet 348: 1596.

  37. 37

    Tanaka, M., Latinne, D., Gianello, P., Sablinski, T., Lorf, T., Bailin, M. et al. 1994. Xenotransplantation from pig to cynomolgus monkey: The potential for overcoming xenograft rejection through induction of chimerism. Transplant Proc. 26: 1326–1327.

  38. 38

    Fryer, J.P., Leventhal, J.R., Dalmasso, A.R., Chen, S., Simone, P.A., Jessurun, J. et al. 1994. Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer. Transpl. Immunol. 2: 87–93.

  39. 39

    Murray, A.G., Khodadoust, M.M., Pober, J.S. and Bothwell, A.L. 1994. Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. Immunity 1: 57–63.

  40. 40

    Kumagai-Braesch, M., Satake, M., Korsgren, O., Andersson, A. and Moller, E. 1993. Characterization of cellular human anti-porcine xenoreactivity. Clin. Transpl. 7: 273–280.

  41. 41

    Yamada, K., Sachs, D.H. and DerSimonian, H. 1995. Direct and indirect recognition of pig class II antigens by human T cells. Transplant Proc. 27: 258–259.

  42. 42

    Yamada, K., Seebach, J.D., DerSimonian, H. and Sachs, D.H. 1996. Human anti-pig T-cell mediated cytotoxicity. Xenotransplantation 3: 179–187.

  43. 43

    Sachs, D.H., Winn, H.J. and Russell, R.S. 1971. The immunologic response to xenografts. Recognition of mouse H-2 histocompatibility antigens by the rat. J. Immunol. 107: 481–492.

  44. 44

    Helg, C., Chapuis, B., Bolle, J.F., Morel, P., Salomon, D., Roux, E., Antonioli, V., Jeannet, M. and Leski, M. 1994. Renal transplantation without immunosuppression in a host with tolerance induced by allogeneic bone marrow transplantation. Transplantation 58: 1420–1422.

  45. 45

    Jacobsen, N., Taaning, E., Ladefoged, J., Kristensen, J.K. and Pedersen, F.K. 1994. Tolerance to an HLA-B, DR disparate kidney allograft after bone-marrow transplantation from same donor [letter]. Lancet 343: 800.

  46. 46

    Sayegh, M.H., Fine, N.A., Smith, J.L., Rennke, H.G., Milford, E.L. and Tilney, N.L. 1991. Immunologic tolerance to renal allografts after bone-marrow transplants from the same donors. Ann. Intern. Med. 114: 954–955.

  47. 47

    lldstad, S.T. and Sachs, D.H. 1984. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature 307(5947):168–170

  48. 48

    Sharabi, Y. and Sachs, D.H. 1989. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J. Exp. Med. 169: 493–502.

  49. 49

    Sharabi, Y., Abraham, V.S., Sykes, M. and Sachs, D.H. 1992. Mixed allogeneic chimeras prepared by a non-myeloablative regimen: requirement for chimerism to maintain tolerance. Bone Marrow Transplant 9: 191–197.

  50. 50

    Blackman, M., Kappler, J. and Marrack, P. 1990. The role of the T cell receptor in positive and negative selection of developing T-cells. Science 248: 1335–1341.

  51. 51

    Inaba, M., Inaba, K., Hosono, M., Kumamoto, T., Ishida, T., Muramatsu, S. et al. 1991. Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells. J. Exp. Med. 173: 549–559.

  52. 52

    Kawai, T., Cosimi, A.B., Colvin, R.B., Powelson, J., Eason, J., Kozlowski, T. et al. 1995. Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation 59: 256–262.

  53. 53

    Sharabi, Y., Aksentijevich, I., Sundt, T.M. III, Sachs, D.H., and Sykes, M. 1990. Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen. J. Exp. Med. 172: 195–202.

  54. 54

    Thomas, F.T., Tepper, M.A., Thomas, J.M. and Haisch, C.E., and Haisch, C.E. 1993. 15-Deoxysper-gualin: a novel immunosuppressive drug with clinical potential. Ann NY Acad. Sci. 685: 175–192.

  55. 55

    Hawley, R.J., Akiyoshi, D.E., Arduini, R., Denaro, M., Dickerson, M., Meshulam, D.H. et al. 1997. Xenogeneic bone marrow transplantation I: Cloning, expression and species specificity of porcine IL-3 and granulocyte-macrophage colony stimulating factor. Xenotransplantation.In press.

  56. 56

    Giovino, M.A., Hawley, R.J., Dickerson, M.W., Glaser, R., Meshulum, D.H., Arduini, R. et al. 1997. Xenogeneic bone marrow transplantation II: Porcine specific growth factors enhance porcine bone marrow engraftment in an in vitro primate microenvironment. Submitted for publication

  57. 57

    Sachs, D.H., Sykes, M., Greenstein, J.L. and Cosimi, A.B. 1995. Tolerance and xenograft survival. Nature Medicine 1: 969.

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