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Immunotherapy of insulin-dependent diabetes mellitus: Tolerance after short-term anti—;IL-2 receptor/cyclosporine therapy in BB/OK rats

  • Chapter
Lessons from Animal Diabetes VI

Part of the book series: Rev.Ser.Advs.Research Diab.Animals (Birkhäuser) ((RSARDA,volume 6))

Abstract

There is convincing evidence that the destruction of pancreatic B-cells leading to insulin-dependent diabetes mellitus (IDDM) is immunologically mediated1–3 and occurs in all mammals.4 Investigations of animal strains predominantly used in diabetes research, the NOD mouse and the BB rat, demonstrated that the acute onset of hyperglycemia is the final result of a chronic preclinical phase (prediabetes). Already during prediabetes and definitely at the onset of the disease, the number of pancreatic B-cells is reduced.5–11 In addition to the diminished number of B-cells, the pancreatic islets of prediabetic or newly diagnosed diabetic animals or patients are characterized by an invasion of immunocytes, so-called insulitis.5,6,9–14 The immunocytochemistry of invading mononuclear cells (MNC) reveals the presence of all major subsets, such as T-lymphocytes (CD4 and CD8 T-cells), B-lymphocytes, macrophages, and NK-cells.8,10–15 Electron microscopic investigations of inflafhed pancreatic islets demonstrated a close contact between immune cells and pancreatic B-cells. As a result of B-cell destruction, B-cell granules have been observed in the extracellular space.15–17 Although the molecular mechanism of B-cell killing is still not established, cytotoxic reactivities of CD4 T-cells,18 CD8 T-cells,19 NK cells,20 and macrophages21 against pancreatic B-cells have been demonstrated. In addition, it has been shown that the secretory products of immunocytes, the cytokines, may directly disrupt B-cells,22 or may induce surface proteins as MHC-antigens or adhesion molecules, which allow or facilitate cell-mediated killing of B-cells.23

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Authors and Affiliations

  1. Institute of Diabetes “G. Katsch”, Medical School, University of Greifswald, Karlsburg, Germany

    Beate Kuttler, Silke Lucke, Lutz Vogt, Ingrid Klöting, Tibor Diamanstein & Prof. Dr. Hans-Jürgen Hahn

  2. Institute of Immunology, Medical School, Free University Berlin, Federal Republic of Germany

    Beate Kuttler, Silke Lucke, Lutz Vogt, Ingrid Klöting, Tibor Diamanstein & Prof. Dr. Hans-Jürgen Hahn

  3. Nepziner Weg 14m, D-17495, Karlsburg, Germany

    Prof. Dr. Hans-Jürgen Hahn & Prof. Dr. Hans-Jürgen Hahn

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  1. Beate Kuttler
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  6. Prof. Dr. Hans-Jürgen Hahn
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  1. Department of Biochemistry, Hadassah Medical Center, POB 12000, IL 91120, Jerusalem, Israel

    Eleazar Shafrir

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Kuttler, B., Lucke, S., Vogt, L., Klöting, I., Diamanstein, T., Hahn, HJ. (1996). Immunotherapy of insulin-dependent diabetes mellitus: Tolerance after short-term anti—;IL-2 receptor/cyclosporine therapy in BB/OK rats. In: Shafrir, E. (eds) Lessons from Animal Diabetes VI. Rev.Ser.Advs.Research Diab.Animals (Birkhäuser), vol 6. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4112-6_4

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