Advertisement

Developments in Immunosuppression The Secret to the Success of Organ Transplantation

  • Charles T. Van Buren

Abstract

For centuries, surgeons have operated on patients in order to remove diseased tissues or to manage traumatic injuries. The objectives of practitioners of such an extirpative discipline became to minimize the surgical tissue loss or to adapt the patient to a regrettable but necessary disability. Only during the twentieth century has the focus of surgery expanded from ablation of disease and shifted toward the restoration of lost function by transplanting living and normally functioning tissues and organs from one individual to another. The success of clinical transplantation has been limited by the transplant surgeon’s understanding of the body’s immune response to transplanted tissues and by effective modulation of this response through suppression of the immune system. An understanding of the history of clinical immunosuppression enables one to understand both the limitations and the future of clinical organ transplantation.

Keywords

Renal Allograft Allograft Survival Renal Allograft Recipient Mixed Lymphocyte Culture Thoracic Duct Lymph 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alexander, J. W., Vaughn, W. K., and Pfaff, W. W., 1987, Local use of kidneys with poor HLA matches is as good as shared use with good matches in the cyclosporine era: An analysis of one and two years, Transplant. Proc. 19: 672–674.PubMedGoogle Scholar
  2. Anderson, C. B., Sicardo, G. A., and Etheredge, E. E., 1982, Pretreatment of renal allograft recipients with azathioprine and donor-specific blood products, Surgery 92: 315–321.PubMedGoogle Scholar
  3. Billingham, R. E., Brent, L., and Medawar, P. B., 1953, Actively acquired tolerance of foreign cells, Nature (Lond.) 172: 603–606.CrossRefGoogle Scholar
  4. Borel, J. F., Feurer, C., Gubler, H. V., and Stahelin, H., 1976, Biological effects of cyclosporin A; a new antilymphocytic agent, Agents Actions 6: 468–475.PubMedCrossRefGoogle Scholar
  5. Caine, R. Y., Alexandre, G. P. J., and Murray, J. E., 1962, A study of the effects of drugs in prolonging survival of homologous renal transplants in dogs, NY Acad. Sci. 99: 743–761.Google Scholar
  6. Caine, R. Y., Rolles, K., White, D. J., Thiru, S., Evans, D. B., McMaster, P., Dunn, D. C., Craddock, G. N., Henderson, R. G., Aziz, S., and Lewis, P., 1979, Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers, Lancet 2: 1033–1039.Google Scholar
  7. Canadian Multicentre Transplant Study Group, 1983, A randomized clinical trial of cyclosporin in cadaveric renal transplantation, N. Engl. J. Med. 309: 809–815.CrossRefGoogle Scholar
  8. Carrel, A., 1910, Remote results of the replantation of the kidney and the spleen, J. Exp. Med. 12: 146–150.PubMedCrossRefGoogle Scholar
  9. Cecka, J. M., Cicciarelli, J., Mickey, M. R., and Terasaki, P. I., 1988, Blood transfusions and HLA matching—an either/or situation in cadaveric renal transplantation, Transplantation 45: 81–86.PubMedCrossRefGoogle Scholar
  10. Cleary, M. L., Warnke, R., and Sklar, J., 1984, Monoclonality of lymphoproliferative in cardiac transplant recipients, N. Engl. J. Med. 310: 477–482.PubMedCrossRefGoogle Scholar
  11. Cupps, T. R., and Fauci, A. S., 1982, Corticosteroid-mediated immunoregulation in man, Immunolog. Rev. 65: 133–155.CrossRefGoogle Scholar
  12. Dupont, E., Wybran, J., and Toussaint, C., 1984, Glucocorticoids and organ transplantation, Transplantation 37: 331–335.PubMedCrossRefGoogle Scholar
  13. Elzinga, L., Kelley, V. E., Houghton, D. C., and Bennett, W. M., 1987, Modification of experimental nephrotoxicity with fish oil as the vehicle for cyclosporine, Transplantation 43: 271–274.PubMedCrossRefGoogle Scholar
  14. English, T. A., McGregor, C., Wallwork, J., and Cory-Pearce, R., 1982, Aspects of immunosuppression for cardiac transplantation, Heart Transplant. 1: 280–284.Google Scholar
  15. European Multicentre Trial Group, 1983, Cyclosporin in cadaveric renal transplantation: One year followup of a Multicentre Trial, Lancet 2: 986–989.CrossRefGoogle Scholar
  16. Flechner, S. M., Kerman, R. H., Van Buren, C. T., and Kahan, B. D., 1984a, Successful transplantation of cyclosporine treated haploidentical living related renal recipients without blood transfusions, Transplantation 37: 73–76.CrossRefGoogle Scholar
  17. Flechner, S. M., Van Buren, C. T., Kerman, R. H., and Kahan, B. D., 1984b, The nephrotoxicity of cyclosporine in renal transplant recipients, Transplant. Proc. 15: 2689–2694.Google Scholar
  18. Franksson, C., Lundgren, G., Magnusson, G., and Rigden, O., 1976, Drainage of thoracic duct lymph in renal transplant patients, Transplantation 21: 133–140.PubMedCrossRefGoogle Scholar
  19. Frazier, O. H., Macris, M. P., Duncan, J. M., Van Buren, C. T., and Cooley, D. A., 1988, Cardiac transplantation in patients over 60 years of age, Ann. Thorac. Surg. 45: 129–132.PubMedCrossRefGoogle Scholar
  20. Fuks, Z., Strober, S., Bobrove, A. M., Sasazuki, T., McMichael, A., and Kaplan, H. S., 1976, Long term effects of radiation on T and B lymphocytes in peripheral blood of patients with Hodgkin’s disease, J. Clin. Invest. 58: 803–814.PubMedCrossRefGoogle Scholar
  21. Glassock, R. J., Feldman, D., Reynolds, E. S., Dammin, G. J., and Merrill, J. P., 1968, Human renal isografts: A clinical and pathologic analysis, Medicine (Baltimore) 47: 411–454.CrossRefGoogle Scholar
  22. Kahan, B. D., Kerman, R. H., Wideman, C. A., Flcchncr, S. M., Jarwenko, M., and Van Buren, C. T, 1985, Impact of cyclosporine on renal transplant practice at the University of Texas Medical School at Houston, Am. J. Kidney Dis. 5: 288–295.PubMedGoogle Scholar
  23. Kerman, R. H., Floyd, M., Van Buren, C. T., and Kahan, B. D., 1980, Improved allograft survival of strong immune responder-high risk recipients with adjuvant ATG therapy, Transplantation 30:450–454.PubMedCrossRefGoogle Scholar
  24. Kerman, R. H., Floyd, M., Van Buren, C. T., McConnell, R., McConnell, B. J., and Kahan, B. D., 1981, Correlation of non-specific immune monitoring with rejection or impaired function of renal allografts, Transplantation 32: 16–23.PubMedCrossRefGoogle Scholar
  25. Kerman, R. H., Van Buren, C. T., Lewis, R. M., and Kahan, B. D., 1988a, Successful transplantation of 100 untransfused cyclosporine-treated primary recipients of cadaveric renal allografts, Transplantation45: 37–40.CrossRefGoogle Scholar
  26. Kerman, R. H., Van Buren, C. T., Lewis, R. M., Frazier, O. H., Cooley, D., and Kahan, B. D., 1988b, The impact of HLA A,B, and DR, blood transfusions, and immune responder status on cardiac allograft recipients treated with cyclosporine, Transplantation 45: 333–337.CrossRefGoogle Scholar
  27. Kirkman, R. L., Barrett, L. V., Gaulton, G. N., Kelley, V. E., Ythier, A., and Strom, T., 1985, Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice, J. Exp. Med. 162: 358–362.PubMedCrossRefGoogle Scholar
  28. Kulkarni, S. S., Bhateley, D. C., Zander, A. P., Van Buren, C. T., Rudolph, F. B., Dicke, K. A., and Kulkarni, A. D., 1984, Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide free diet, Exp. Hematol. 12: 629–699.Google Scholar
  29. Kulkarni, A. D., Fanslow, W. C., Rudolph, F. B., and Van Buren, C. T., 1987, Modulation of delayed hypersensitivity in mice by dietary nucleotide restriction, Transplantation 44: 847–849.PubMedGoogle Scholar
  30. Lorber, M. I., Flechner, S. M., Van Buren, C. T., Kerman, R. H., Bartosh, J., and Kahan, B. D., 1985, Cyclosporine toxicity: The effect of combined therapy using cyclosporine, azathioprine, and prednisone, Hum. Immunol. 13: 59–60.Google Scholar
  31. Lorber, M. I., Van Buren, C. T., Flechner, S. M., Williams, C., and Kahan, B. D., 1987, Hepatobiliary and pancreatic complications of cyclosporin therapy in 466 renal transplant patients, Transplantation 43: 35–40.PubMedCrossRefGoogle Scholar
  32. Matas, A. J., Tellis, V. A., Quinn, T. A., Glicklich, D., Soberman, R., and Veith, F. J., 1988, Individualization of immediate posttransplant immunosuppression, Transplantation 45: 406–409.PubMedCrossRefGoogle Scholar
  33. Merrill, J. P., Murray, J. E., Harrison, J. H., and Guild, W. R., 1956, Successful homotransplantation of the human kidney between identical twins, JAMA 160:277–282.CrossRefGoogle Scholar
  34. Murray, J. E., Merrill, J. P., Dammin, G. J., Dealy, J. B., Alexandre, G. W., and Harrison, J. H., 1962, Kidney transplantation in modified recipients, Ann. Surg. 156: 337–355.PubMedCrossRefGoogle Scholar
  35. Myers, B. D., Ross, J., Newton, L., Luetscher, J., and Perlroth, M. 1984, Cyclosporine-associated chronic nephropathy, N. Engl. J. Med. 311: 699–705.PubMedCrossRefGoogle Scholar
  36. Myburgh, J. A., Smith, J. A., Hill, R. R. H., and Browde, S., 1980, Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I1. Renal allograft, Transplantation 29: 405–408.PubMedCrossRefGoogle Scholar
  37. Najarian, J. S., Simmons, R. L., Condie, R. M., Thompson, E. J., Fryd, D. S., Howard, R. J., Matas, A. J., Sutherland, D. E., Ferguson, R. M., and Schmidtke, J. R., 1976, Seven years experience with antilymphoblast globulin for renal transplantation, Ann. Surg. 184: 352–368.PubMedCrossRefGoogle Scholar
  38. Najarian, J. S., Ferguson, R. M., Sutherland, D. E., Slavin, S., Kim, T., Kersey, J., and Simmons, R. L.. 1982, Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation, Ann. Surg. 196: 442–452.PubMedCrossRefGoogle Scholar
  39. Najarian, J. S., Fryd, G. S., Strand, M., Canafax, D. M., Ascher, N. L., Dayne, W. D., Simmons, R. L., and Sutherland, D. E., 1985, A single-institution, randomized, prospective trial of cyclosporine versus azathioprine-antilymphocyte globulin for immunosuppression in renal allograft recipients, Ann. Surg. 201: 142–157.PubMedCrossRefGoogle Scholar
  40. Okazaki, H., Maki, T., Wood, M., and Monoco, A. P., 1980, Effect of a single transfusion of donor specific and nonspecific blood on skin allograft survival in mice, Transplantation 30: 421–428.PubMedCrossRefGoogle Scholar
  41. Opelz, G., Sengar, D. P., Mickey, M. R., and Terasaki, P. I., 1973, Effect of blood transfusions on subsequent kidney transplants, Transplant. Proc. 5: 253–259.PubMedGoogle Scholar
  42. Opelz, G., 1987, Improved kidney graft survival in nontransfused recipients, Transplant. Proc. 19: 149–152.PubMedGoogle Scholar
  43. Penn, I., 1981, Depressed immunity and the development of cancer, Clin. Exp. Immunol. 46: 459–474.PubMedGoogle Scholar
  44. Renlund, O. G., Bristow, M. R., Lybbert, M. R., O’Connell, J. B., and Gay, W. A., 1987, Medicare designated centers for cardiac transplantation, N. Engl. J. Med. 316: 873–876.PubMedCrossRefGoogle Scholar
  45. Reitz, B. A., Wallwork, J. L., Hunt, S. A., Pennock, J. L., Billingham, M. E., Oyer, P. E., Stinson, E. B., and Shumway, M. E., 1982, Heart lung transplantation: Successful therapy for patients with pulmonary vascular disease, N. Engl. J. Med. 306: 557–564.PubMedCrossRefGoogle Scholar
  46. Report of the Task Force on Organ Transplantation, 1986, Organ Transplantation: Issues and Recommendations, U. S. Department of Health and Human Services, Public Health Service, Health Resources and Services Administration, Office of Organ Transplantation, April, 1986.Google Scholar
  47. Salvatierra, O., Vincenti, F., Amend, W., Potter, D., Iwaki, Y., Opelz, G., Terasaki, P., Duca, R., Cochrum, K., Hanes, D., Stoney, R., and Feduska, N., 1980, Deliberate donor-specific blood transfusions prior to living related renal transplantation, Ann. Surg. 192: 543–552.PubMedCrossRefGoogle Scholar
  48. Sampson, O., Levin, B. S., Hoppe, R. T., Bierber, C. P., Miller, E., Waer, M., Kaplan, H. S., Collins, G., and Strober, S., 1985, Preliminary observations on the use of total lymphoid irradiation, rabbit antithymocyte globulin, and low dose prednisone in human cadaver renal transplantation, Transplant. Proc. 17: 1299–1303.Google Scholar
  49. Sanfilippo, F., Vaughn, W. K., Spees, E. K., Light, J., and LeFor, W. M., 1984, Benefits of HLA-A and HLA-B matching on graft and patients. Outcome after cadaver—donor renal transplantation, N. Engl. J. Med. 311: 358–364.PubMedCrossRefGoogle Scholar
  50. Schroeder, J. S., and Hunt, S. A., 1986, Cardiac transplantation: Where are we? N. Engl. J. Med. 315: 961–963.PubMedCrossRefGoogle Scholar
  51. Schwartz, R., and Dameshek, W., 1959, Drug-induced immunological tolerance, Nature (Lond.) 183: 1682–1683.CrossRefGoogle Scholar
  52. Sherlock, S., 1983, Hepatic transplantation: The state of play, Lancet 2: 778–779.PubMedCrossRefGoogle Scholar
  53. Simmons, R. L., Matas, A. J., Rattazzi, L. C., Balfour, H. H., Howard, R. J., and Najarian, J. S., 1977, Clinical characteristics of the lethal cytomegalovirus infection following renal transplantation, Surgery 82: 537–546.PubMedGoogle Scholar
  54. Smith, M. D., Williams, J. D., Coles, G. A., and Salaman, J.R., 1981, The effect of blood transfusion on T suppressor cells in renal dialysis patients, Transplant. Proc. 13: 181–183.PubMedGoogle Scholar
  55. Sollinger, H. W., Stratta, R. J., Kalayoglu, M., Pirsch, J. D., and Belzer, F. O., 1987, Pancreas transplantation with pancreaticocystostomy and quadruple immunosuppression, Surgery 102: 674–679.PubMedGoogle Scholar
  56. Spees, E. K., Vaughn, W. K., Williams, G. M., Filo, R. S., MacDonald, J. C., Mendez-Picon, G., and Niblack, G., 1980, Effects of blood transfusion on cadaver renal transplantation, Transplantation 30: 455–463.PubMedCrossRefGoogle Scholar
  57. Starzl, T. E., Marchioro, T. L., Porter, K. A., and Brettschneider, L., 1967, The liver: Homotransplantation of the liver, Transplantation 5: 790–803.PubMedCrossRefGoogle Scholar
  58. Starzl, T. E., Groth, C.G., Putnam, C. W., Corman, J., Halgrimson, C. G., Penn, I., Husberg, B., Gustafsson, A., Cascardo, S., Geis, P., and Iwatsuki, S., 1973, Cyclophosphamide for clinical renal and hepatic transplantation, Transplant. Proc. 5: 511–516.PubMedGoogle Scholar
  59. Starzl, T. E., Iwatsuki, S., Klintmalm, G., Schroter, G. P., Weil, R., Koep, L. T., and Porter, K. A., 1981, Liver transplantation 1980, with particular reference to cyclosporin A, Transplant. Proc. 18: 281–285.Google Scholar
  60. Thistlethwaite, J. R., Gaber, A. O., Haag, B. W., Aronson, A. J., Broelsch, C. E., Stuart, J. K., and Stuart, F. P., 1987, OKT3 treatment of steroid-resistant renal allograft rejection, Transplantation 43: 176–184.PubMedCrossRefGoogle Scholar
  61. Tilney, N. L., Strom, T. B., Vineyard, G. C., and Merrill, J. P., 1978, Factors contributing to the declining mortality rate in renal transplantation, N. Engl. J. Med. 299: 1321–1325.PubMedCrossRefGoogle Scholar
  62. Toronto Lung Transplant Group, 1986, Unilateral lung transplantation for pulmonary fibrosis, N. Engl. J. Med. 314: 1140–1145.CrossRefGoogle Scholar
  63. Van Buren, C. T., Kulkarni, A. D., and Rudolph, F. B., 1983a, Synergistic effect of a nucleotide-free diet and cyclosporine on allograft survival, Transplant. Proc. 15(suppl 2): 2967–2968.Google Scholar
  64. Van Buren, C. T., Kulkami, A., Schandle, B. V., and Rudolph, F. B., 1983b, The influence of dietary nucleotides on cell mediated immunity, Transplantation 36: 350–352.CrossRefGoogle Scholar
  65. Van Buren, C. T., Kulkarni, A. D., Fanslow, W. C., and Rudolph, F. B., 1985, Dietary nucleotides: A requirement for helper/inducer T lymphocytes, Transplantation 40: 694–697.PubMedCrossRefGoogle Scholar
  66. Van Buren, C. T., Kim, E. E., Kulkarni, A. D., Fanslow, W. L., and Rudolph, F B.. 1987, Nucleotide free diet and suppression of the immune response, Transplant. Proc. 19: 57–59.PubMedGoogle Scholar
  67. Watson, D. C., Reitz, B. A., Oyer, P. E., Stinson, E. B., and Shumway, N. E., 1980, Sequential orthotopic heart transplantation in man, Transplantation 30: 401–403.PubMedCrossRefGoogle Scholar
  68. Zukoski, C. F., Callaway, J. M., and Rhea, W. G., 1965, Prolonged acceptance of canine renal allograft achieved with prednisolone, Transplantation 3: 380–386.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Charles T. Van Buren
    • 1
  1. 1.Division of Immunology/Organ TransplantationUniversity of Texas Medical School at HoustonHoustonUSA

Personalised recommendations