Abstract
The reversal of insulin-dependent diabetes mellitus (IDDM) by allogeneic islet transplantation without immunosuppression is the goal of experimental transplantation studies. To accomplish this objective, effective pretreatment methods for the prevention of islet allograft rejection are necessary. Antigen-presenting cells (APC) appear to play an important role in the mechanism of allograft rejection (1,2). APC such as dendritic cells and macrophages are widely distributed in various tissues, including islets (3,4). They express major histocompatibility complex (MHC) class II antigens, originally referred to in rodents as Ia antigens (5–8). Destruction or functional alteration of APC by incubation of islet allografts with antibody against MHC class II antigens and complement (9,10) or combined treatment with ultraviolet light and 8-methoxypsoralen (PUVA) prior to transplantation are possible methods for the reduction of APC-mediated immunogenicity. In order to prevent damage of endocrine cells by the pretreatment procedure, experimental conditions have to be created for the preservation of β-cell specific function. Therefore, the present study examines the influence of the above manipulations on islet function before transplantation and on survival of islet grafts after transplantation in the LEW rat model.
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References
Charpentier B: Mechanisms of rejection: Update 1982. Transplant Proc 1983; 15:259–263.
Mason DW: The mechanism of allograft rejection—progress and problems. Transplant Proc 1983; 15:264–268.
Hart DNJ, Fabre JW: Demonstration and characterization of la-positive dendritic cells in the interstitial connective tissue of rat heart and other tissues, but not brain. J Exp Med 1981;154:347–361.
Ulrichs K, Müller-Ruchholtz W: MHC class II antigen expression on the various cells of normal and activated isolated pancreatic islets. Diagn Immunol 1985;3:47–55.
Steinman RM, Witmer MD, Nussenzweig MC, et al: Studies with a monoclonal antibody to mouse dendritic cells. Transplant Proc 1983;15:299–310.
Nussenzweig MC, Steinman RM, Witmer MD, Gutchinov B: A monoclonal antibody specific for mouse dendritic cells. Proc Natl Acad Sci USA 1982;79:161–165.
Steinman RM, Nussenzweig MC: Dendritic cells: Features and functions. Immunol Rev 1980;53:127–147.
Steinman RM, Witmer MD: Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci USA 1978;75:5132–5136.
Faustman DL, Steinman RM, Gebel RM, et al: Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci USA 1984;81:3864–3868.
Faustman DL, Hauptfeld V, Lacy PE, Davie JM: Prolongation of murine islet allograft survival by pretreatment of islets with antibody directed to Ia determinants. Proc Natl Acad Sci USA 1981;78:5156–5159.
Wilson JD, Prowse SJ, Haynes SP: Pancreatic islet allograft function in non-immunosuppressed conscious mice. Metabolism 1985;34:92–95.
Bowen KM, Lafferty KJ: Reversal of diabetes by allogeneic islet transplantation without immunosuppression. Aust J Exp Biol Med Sci 1980;58:441–447.
Morrow CE, Sutherland DER, Steffes MW, et al: H-2 antigen class: Effect on mouse islet allograft rejection. Science 1983;219:1337–1339.
Lacy PE, Kostianovsky: Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 1967;16:35–39.
Schmidt S, Wilke B, Klöting I: Photochemical (PUVA) treatment of isolated rat islets. Biomed Biochim Acta 1984;43:703–710.
Wilke B, Ziegler B, Schmidt S, et al: The influence of cultivation on (pro)insulin biosynthesis and secretion of isolated pancreatic islets of C57BL-mice, long-term treated with glibenclamide in vivo. Endokrinologie 1980;76:357–364.
Jahr H, Schröder D, Ziegler B, et al: Transcriptional and translational control of glucose-stimulated (pro)insulin biosynthesis. Eur J Biochem 1980; 110: 499–505.
Gottschling HD, Ziegler M, Wilke W, Michael R: Radioimmunoassay von Plasmainsulin. Methodenkritische Untersuchungen. Radiobiol Radiother (Berl) 1974;15:85–89.
Fox IJ, Perry LL, Sy MS, et al: The influence of ultraviolet light irradiation on the immune system. Clin Immunol Immunopathol 1980;17:141–155.
Spellman CW, Tornasi TB: Ultraviolet light-induced suppression of antigen presentation. J Clin Immunol 1983;3:105–110.
Norlund JJ, Ackles AE, Lerner AB: The effects of ultraviolet light and certain drugs on Ia-bearing Langerhans cells in murine epidermis. Cell Immunol 1981;60:50–63.
Gruner S, Meffert H, Karasek E, Sönnichsen N: Prolongation of skin graft survival in mice by in vitro PUVA treatment and failure of induction of specific immunological memory by PUVA-treated grafts. Arch Dermatol Res 1984;276:82–85.
Gruner S, Riese C, Schnitzler S, et al: Prolongation of the survival of skin grafts in mice by PUVA treatment. Experientia 1984;40:487–488.
Baekkeskov S, Kanatsuna T, Klareskog L, et al: Expression of major histocompatibility antigens on pancreatic islet cells. Proc Natl Acad Sci USA 1981;78:6456–6460.
Faustman D, Hauptfeld V, Davie JM, et al: Murine Pancreatic β-cells express H-2K and H-2D but not Ia antigens. J Exp Med 1980;151:1563–1568.
Parr EL, Oliver JR, King NJC: The surface concentration of H-2 antigens on mouse pancreatic β-cells and islet cell transplantation. Diabetes 1982;31(suppl 4):1–8.
Parr EL, Lafferty KJ, Bowen KM, McKenzie JFC: H-2 complex and Ia antigens on cells dissociated from mouse thyroid glands and islets of Langerhans. Transplantation 1980;30:142–148.
Hart DNJ, Newton MR, Reece-Smith H, et al: Major histocompatibility complex antigens in the rat pancreas, isolated pancreatic islets, thyroid and adrenal. Transplantation 1983;36:431–435.
Kuttler B, Klöting I, Schmidt S: Cytotoxicity of MHC antisera against rat islets: detection by release of 51Cr and leakage of hormones. Diabetes Res 1985;2:77–80.
Jahr H, Kruschel B, Walter BM, Kohnert KD: Complement-mediated cytotoxic effects of islet cell surface antibodies: factors influencing the sensitivity of the target cells. Biomed Biochim Acta 1984;43:641–646.
Prowse SJ, Lafferty KJ, Simeonovic CJ, et al: The reversal of diabetes by pancreatic islet transplantation. Diabetes 1982;31(suppl 4):30–37.
Malkovsky M, Medawar PB: Is immunological tolerance (non-responsiveness) a consequence of interleukin 2 deficit during the recognition of antigen? Immunol Today 1984;5:340–343.
Lau H, Reemtsma K, Hardy MA: Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft. Science 1984;223:607–608.
Tucker K, Suzuki M, Waldeck NJ, et al: Successful rat pancreatic islet allotransplantation without recipient immunosuppression. Cell Immunol 1983;79:403–406.
Terasaka R, Lacy PE, Hauptfeld V, et al: The effect of cyclosporin-A, low-temperature culture, and anti-la antibodies on prevention of rejection of rat islet allografts. Diabetes 1986;35:83–88.
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© 1988 Springer-Verlag New York Inc.
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Schmidt, S., Wilke, B., Kuttler, B., Klöting, I. (1988). Islet Graft Pretreatment with PUVA or Antibodies to MHC Antigens. In: Peterson, C.M., Jovanovic-Peterson, L., Formby, B. (eds) Fetal Islet Transplantation. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3766-2_6
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DOI: https://doi.org/10.1007/978-1-4612-3766-2_6
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