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Pancreatic Islet Transplantation

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Molecular Biology of Diabetes

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Abstract

Type I diabetes represents a unique problem for the field of transplantation. The rationale for pancreatic islet grafting is to prevent the debilitating complications associated with the disease process. Indeed, islet transplantation has been shown to prevent or arrest diabetic complications (1–3). However, unlike other conditions of end-stage organ failure where transplantation is necessary, diabetes is not immediately life-threatening with the advent of exogenous insulin therapy. Thus, for type I diabetes, the risks associated with current regimens of immunosuppression used in transplantation, such as nephrotoxicity, opportunistic infections, and neoplasia, may rival the consequences of disease-associated complications. Therefore, the criteria for islet transplantation in diabetic recipients prior to the manifestations of disease complications must be more stringent than those for patients with other forms of organ failure. This problem is reflected by the current status of clinical islet transplantation where islet grafts are usually performed in diabetic patients receiving simultaneous solid organ grafts (usually kidney) with concomitant immunosuppression (4). The future goal of islet transplantation, however, must be the grafting of islets in the diabetic recipient prior to the onset of disease complications using minimal host immunosuppression.

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References

  1. Gray BN, Watkins E: Prevention of vascular complications of diabetes by pancreatic islet transplantation. Arch Surg 111:254–257, 1976.

    Article  Google Scholar 

  2. Federlin KF, Bretzel RG: The effect of islet transplantation on complications in experimental diabetes of the rat. World J Surg 8:169–178, 1984.

    Article  Google Scholar 

  3. Woehrle M, Spitzer D, Linn T, Federlin K, Bretzel RG: The effect of early islet transplantation on prevention of nephropathy in the spontaneously diabetic BB rat. Transplant Proc 22:819–820, 1990.

    Google Scholar 

  4. Warnock GL, Rajotte RV: Human pancreatic islet transplantation. Transplant Rev 6:195–208, 1992.

    Article  Google Scholar 

  5. Sutherland DER, Sibley R, Xu XZ, Srikanta MS, Taub F, Najarian J, Goetz FC: Twin-to-twin pancreas transplantation: reversal and reenactment of the pathogenesis of type I diabetes. Trans Assoc Am Phys 97:80–87, 1984.

    Google Scholar 

  6. Terada M, Lennartz K, Mullen Y: Allogeneic and syngeneic pancreas transplantation in non-obese diabetic mice. Transplant Proc 19:960–961, 1987.

    Google Scholar 

  7. Naji A, Silvers WK, Kimura H, Anderson AO, Barker CF: Influence of islet and bond marrow transplantation on the diabetes and immunodeficiency of BB rats. Metabolism 32(Suppll):62–68, 1983.

    Article  Google Scholar 

  8. Calcinaro F, Wegmann DR, Lafferty KJ: Pathogenesis of Autoimmune Diabetes (in this volume).

    Google Scholar 

  9. Medawar PB: The Uniqueness of the Individual (2nd rev ed), Dover, New York, pp. 1–155, 1957.

    Google Scholar 

  10. Snell GD: The homograft reaction. Ann Rev Microbiol 11:439–458, 1957.

    Article  Google Scholar 

  11. Batchelor JR, Welsh K, Burgos H: Transplantation antigens per se are poor immunogens within a species. Nature 273:54–56, 1978.

    Article  Google Scholar 

  12. Lafferty KJ, Cunningham AJ: A new analysis of allogeneic interactions Aust J Exp Biol Med Sci 53:27–42, 1975.

    Article  Google Scholar 

  13. Bretscher P, Cohn M: A theory of self-nonself discrimination. Science 169:1042–1049, 1970.

    Article  Google Scholar 

  14. Talmage DW, Woolnough JA, Hemmingsen H, Lopez L, Lafferty KJ: Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s). Proc Natl Acad Sci USA 74:1610–1614, 1977.

    Article  Google Scholar 

  15. June CH, Ledbetter JA, Linsley PS, Thompson CB: Role of the CD28 receptor in T-cell activation. Immunol Today 11:211–216, 1990.

    Article  Google Scholar 

  16. Linsley PS, Brady W, Urnes M, Grosmarie LS, Damle NK, Ledbetter JA: CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 174:561–569, 1991.

    Article  Google Scholar 

  17. Schwartz RH: Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71:1065–1068, 1992.

    Article  Google Scholar 

  18. Kamle NK, Klussman K, Linsley PS, Aruffo A: Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol 148:1985–1992, 1992.

    Google Scholar 

  19. Nabavi N, Freeman GJ, Gault A, Godfrey D, Nadler LM, Glimcher LH: Signalling through the MHC class II cytoplasmic domain is required for antigen presentation and induces B7 expression. Nature 360:266–268, 1992.

    Article  Google Scholar 

  20. Lafferty KJ, Prowse SJ, Simeonovic CJ: Immunobiology of tissue transplantation: a return to the passenger leukocyte concept. Ann Rev Immunol 1:143–173, 1983.

    Article  Google Scholar 

  21. Lafferty KJ, Bootes A, Dart G, Talmage DW: Effect of organ culture on the survival of thyroid allografts in mice. Transplantation 22:138–149, 1976.

    Article  Google Scholar 

  22. Bowen KM, Andrus L, Lafferty KJ: Successful allotransplantation of mouse pancreatic islets to nonimmunosuppressed recipients. Diabetes 29:98–104, 1980.

    Google Scholar 

  23. Haug CE, Gill RG, Babcock SK, Lafferty KJ, Bellgrau D, Weil RW III: Cyclosporine-induced tolerance requires antigens capable of initiating an immune response. J Immunol 139:2947–2949, 1987.

    Google Scholar 

  24. Simeonovic CJ, Prowse SJ, Lafferty KJ: Survival and function of islet allografts in outbred mice. Transplant Proc 18:316–318, 1986.

    Google Scholar 

  25. Lau H, Reemtsma K, Hardy MA: Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft. Science 223:607–608, 1984.

    Article  Google Scholar 

  26. Lacy PE, Davie JM, Finke EH, Scharp DW: Prolongation of islet allograft survival. Transplantation 27:171–174, 1979.

    Article  Google Scholar 

  27. Faustman D, Hauptfeld V, Lacy P, Davie J: Prolongation of murine islet allograft survival by pretreatment of islets with antibody directed to Ia determinants. Proc Natl Acad Sci USA 78:5156–5159, 1981.

    Article  Google Scholar 

  28. Morrow CE, Sutherland DER, Steffes MW, Najarian JS, Bach FH: Lack of donor-specific tolerance in mice with established anti-la-treated islet allografts. Transplantation 36:691–694, 1983.

    Article  Google Scholar 

  29. Faustman DL, Steinman RM, Gebel HM, Hauptfeld V, Davie JM, Lacy, PE: Prevention of rejection of murine islet allografts by pretreatment with antidendritic cell antibody. Proc Natl Acad Sci USA 81:3864–3868, 1984.

    Article  Google Scholar 

  30. La Rosa FG: Abrogation of mouse pancreatic islet allograft rejection by a four-day culture. Transplantation 46:330–333, 1988.

    Article  Google Scholar 

  31. Hegre OD, Hickey GE, Marshall S, Serie JR: Modification of allograft immunogenicity in perinatal islets isolated and purified in vitro. Transplantation 37:227–233, 1984.

    Article  Google Scholar 

  32. Hullett DA, Landry AS, Leonard DK, Sollinger HW: Enhancement of thyroid allograft survival following organ culture. Transplantation 47:24–27, 1989.

    Article  Google Scholar 

  33. La Rosa FG, Talmage DW: The abrogation of thyroid allograft rejection by culture in acid medium. Transplantation 44:592, 1987.

    Article  Google Scholar 

  34. Jacobs BB: Ovarian allograft survival. Transplantation 18:454–457,1974.

    Article  Google Scholar 

  35. Punit SR, Sharp RJ, Yeoman H, Stanley MA: The influence of MHC-compatible and MHC-incompatible antigen-presenting cells on the survival of MHC-compatible cultured murine keratinocyte allografts. Transplantation 48:676–680, 1989.

    Google Scholar 

  36. Woodruff MFA, Woodruff HG: The transplantation of normal tissues: with special reference to auto and homotransplants of thyroid and spleen in the anterior chamber of the eye, and subcutaneously, in guinea-pigs. Phil Trans R Soc Lond 234:560–583, 1950.

    Google Scholar 

  37. Jacobs BB, Huseby RA: Growth of tumors in allogeneic hosts following organ culture explantation. Transplantation 5:410–419, 1967.

    Article  Google Scholar 

  38. La Rosa FG, Talmage DW: Major histocompatibility complex antigen expression on parenchymal cells of thyroid allografts is not by itself sufficient to induce rejection. Transplantation 49:605–609, 1990.

    Article  Google Scholar 

  39. Batchelor J, Welsh K, Maynard A, Burgos H: Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. I. Retransplantation of (AS X AUG)F1 kidneys into secondary AS recipients. J Exp Med 150:455–464, 1979.

    Article  Google Scholar 

  40. Lechler RI, Batchelor JR: Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 155:31–41, 1982.

    Article  Google Scholar 

  41. Bowen KM, Prowse SJ, Lafferty KJ: Reversal of diabetes by islet transplantation: vulnerability of the established allograft. Science 213:1261, 1262, 1981.

    Article  Google Scholar 

  42. Vesole DH, Dart GA, Talmage DW: Rejection of stable cultured allografts by active or passive (adoptive) immunization. Proc Natl Acad Sci USA 78:1626–1628, 1982.

    Article  Google Scholar 

  43. Markmann J, Lo D, Naji A, Palmiter RD, Brinster RL, Heber-Katz E: Antigen presenting function of class II MHC expressing pancreatic beta cells. Nature 336:476–479, 1988.

    Article  Google Scholar 

  44. Lo D, Burkly LC, Widera G, Cowing C, Flavell RA, Palmiter RD, Brinster RL: Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell 53:159–168, 1988.

    Article  Google Scholar 

  45. Calne RY: Organ transplantation between widely disparate species. Transplant Proc 2:550, 1970.

    Google Scholar 

  46. Auchincloss HJ: Xenogeneic transplantation: A review. Transplantation 46:1–20, 1988.

    Article  Google Scholar 

  47. Platt JL, Bach FH: The barrier to xenotransplantation. Transplantation 52:937–947, 1991.

    Article  Google Scholar 

  48. Sachs DH, Bach FH: Immunology of xenograft rejection. Hum Immunology 28:245–251, 1990.

    Article  Google Scholar 

  49. Gill RG: The role of direct and indirect antigen presentation in the response to islet xenografts. Transplant Proc 24:642, 643, 1992.

    Google Scholar 

  50. Lafferty KJ, Warren HS, Woolnough JA, Talmage DW: Immunological induction of T lymphocytes: role of antigen and the costimulator. Blood Cells 4: 395–404, 1978.

    Google Scholar 

  51. Alter BJ, Bach FH: Cellular basis of the proliferative response of human T cells to mouse xenoantigens. J Exp Med 171:333–338, 1990.

    Article  Google Scholar 

  52. Moses R, Winn HJ, Auchincloss H Jr: Evidence that multiple defects in cell-surface molecule interactions across species differences are responsible for diminished xenogeneic T cell responses. Transplantation 53:203–209, 1992.

    Article  Google Scholar 

  53. Sprent J: The thymus and T cell tolerance. Today’ s Life Sci 3:14–20, 1991.

    Google Scholar 

  54. Swain SL: T cell subsets and the recognition of MHC class. Immunol Rev 74:129–142, 1983.

    Article  Google Scholar 

  55. von Hoegen P, Miceli MC, Tourvieille B, Schilham M, Parnes JR: Equivalence of human and mouse CD4 in enhancing antigen responses by a mouse class II-restricted T-cell hybridoma. J Exp Med 170:1879–1886, 1989.

    Article  Google Scholar 

  56. Clayton LK, Sieh M, Pious DA, Reinherz EL: Identification of residues affecting class II versus HIV-1 gpl20 binding. Nature 339:548–551, 1989.

    Article  Google Scholar 

  57. Barzaga-Gilbert E, Grass D, Lawrance SK, Peterson PA, Lacy E, Engelhard VHd: Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice J Exp Med 175:1707–1715, 1992.

    Article  Google Scholar 

  58. Irwin MJ, Heath WR, Sherman LA: Species-restricted interactions between CD8 and the α3 domain of class I influence the magnitude of the xenogeneic response. J Exp Med 170:1091–1101, 1989.

    Article  Google Scholar 

  59. Kalinke U, Arnold B, Hammerling GJ: Strong xenogeneic HLA response in transgenic mice after introducing an a3 domain into HLA B27. Nature 348:642–644, 1990.

    Article  Google Scholar 

  60. Greenstein JL, Foran JA, Gorga JC, Burakoff SJ: The role of T cell accessory molecules in the generation of class II-specific xenogeneic cytolytic T cells. J Immunol 136:2358–2363, 1986.

    Google Scholar 

  61. Golding H, Singer A: Role of accessory cell processing and presentation of shed H-2 alloantigens in allospecific cytotoxic T lymphocyte responses. J Immunol 133:597, 1984.

    Google Scholar 

  62. Yoshizawa K, Yano A: Mouse T lymphocytes proliferative responses specific for human MHC products in mouse anti-human xenogeneic MLR. J Immunol 132:2820–2829.

    Google Scholar 

  63. Brunswick M, Lake P: Functional interactions of human and murine lymphoid cells. Cell Immunol 103:441–454, 1986.

    Article  Google Scholar 

  64. Pierson RN III, Winn HJ, Russell PS, Auchincloss H: Xenogeneic skin graft rejection is especially dependent on CD4+ T cells. J Exp Med 170:991–996, 1989.

    Article  Google Scholar 

  65. Mandel TE, Koulmanda M, Loudovaris T, Bacelj A: Islet grafts in NOD mice: a comparison of iso-, allo-, and pig xenografts. Transpl Proc 21:3813, 3814, 1989.

    Google Scholar 

  66. Gill RG, Coulombe M: Rejection of pancreatic islet xenografts does not require CD8+ T-lymphocytes. Transplant Proc 24:2877, 2878, 1992.

    Google Scholar 

  67. Shizuru JA, Gregory AK, Chao CTB, Fathman CG: Islet allograft survival after a single course of treatment of recipient with antibody to L3T4. Science 237:278–280, 1987.

    Article  Google Scholar 

  68. Hao L, Wang Y, Gill RG, Lafferty KJ: Role of the L3T4+ T cell in allograft rejection. J Immunol 139:4022–4026, 1987.

    Google Scholar 

  69. Lacy PE, Ricordi C, Finke EH: Effect of transplantation site and αL3T4 treatment on survival of rat, hamster, and rabbit islet xenografts in mice. Transplantation 47:761–766, 1989.

    Article  Google Scholar 

  70. Ricordi C, Lacy PE, Sterbenz K, Davie JM: Low-temperature culture of human islets or in vivo treatment with L3T4 antibody produces a marked prolongation of islet human-to-mouse xenograft survival. Proc Natl Acad Sci USA 84:8080–8084, 1987.

    Article  Google Scholar 

  71. Gill RG, Lafferty KJ: The role of islet transplantation in the treatment of insulin-dependent diabetes mellitus. Immunol Allergy ClinNorth Am 9:165–186, 1989.

    Google Scholar 

  72. Wang Y, Pontesili O, Gill RG, La Rosa FG, Lafferty KJ: The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice. Proc Natl Acad Sci USA 88:527–531, 1991.

    Article  Google Scholar 

  73. Desai NM, Bassiri H, Odorico JS, Koller BH, Smithies O, Naji A, Barker CF, Markmann JF: Pancreatic islet allograft and xenograft survival in CD8+ T-lymphocyte-deficient recipients. Transplant Proc 25:961, 962, 1993.

    Google Scholar 

  74. Mandel TE, Koulmanda M: The survival of xeno-, allo-and isografts in NOD mice and xenografts in other strains, after immunosuppression with anti-CD4 monoclonal antibody. Diabetes Nutr Metab 5(Suppl l):91–96, 1992.

    Google Scholar 

  75. Simeonovic CJ, Wilson JD: CD4+ T-cell depletion in mice facilitates induction of tolerance to pig proislet xenografts: a comparison of NOD and CBA/H recipient models. Diabetes Nutr Metab 5(Suppl 1):133–138, 1992.

    Google Scholar 

  76. Haskins K, Portas M, Bergman B, Lafferty K, Bradley B: Pancreatic islet-specific T-cell clones from nonobese diabetic mice. Proc Natl Acad Sci USA 86:8000–8004, 1989.

    Article  Google Scholar 

  77. Lenchow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA: Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA41g. Science 257:789–792, 1992.

    Article  Google Scholar 

  78. Carel J-C, Schreiber RD, Falqui L, Lacy PE: Transforming growth factor b decreased the immunogenicity of rat islet xenografts (rat to mouse) and prevents rejection in association with treatment of the recipient with a monoclonal antibody to interferon g. Proc Natl Acad Sci USA 87:1591–1595, 1990.

    Article  Google Scholar 

  79. Faustman D, Coe C: Prevention of xenograft rejection by masking donor HLA class I antigens. Science 252:1700–1702, 1991.

    Article  Google Scholar 

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  1. Ronald G. Gill
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Editors and Affiliations

  1. University of Colorado Health Sciences Center, Denver, CO, USA

    Boris Draznin MD, PhD

  2. National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA

    Derek LeRoith MD, PhD

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Gill, R.G. (1994). Pancreatic Islet Transplantation. In: Draznin, B., LeRoith, D. (eds) Molecular Biology of Diabetes. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0241-7_3

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  • DOI: https://doi.org/10.1007/978-1-4612-0241-7_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6677-8

  • Online ISBN: 978-1-4612-0241-7

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