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Cellular cytotoxicity to membrane-associated insulin in an autologous system

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Summary

A method is described for the measurement of T-cell cytotoxicity to purified preparations of insulin, their high molecular weight fractions and C-peptide derivatives. The technique assesses cellular cytotoxicity to membrane associated insulin in an autologous system. Peripheral blood lymphocytes from 19 type 1 diabetic patients were stimulatedin vitro for 6 days with the pharmaceutical preparation(s) used therapeutically. At the end of this period, they were set up in a 4-h cytotoxicity assay against51Cr labelled PHA blast transformed lymphocytes in the presence of therapeutic insulin, monocomponent insulin, B-component or C-peptide. The results presented here demonstrate cytotoxicity to insulin B-component in diabetic patients who have received pork insulin for 2–6 years. The possible reasons for this finding are discussed.

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References

  1. Bertrams J., Jansen F. K., Gruneklee D., Reiss H. E., Drost H., Beyer J., Gries F. A., Kuwert E.: HLA-antigens and the immunoresponsiveness to insulin in insulin-dependent diabetes mellitus — Tissue Antigens8, 13, 1976.

    Article  PubMed  CAS  Google Scholar 

  2. Chance R. E., Root M. A., Galloway J. A.: The immunogenicity of insulin preparations — Acta endocrinol. (Khb.)83 (Suppl. 205), 185, 1976.

    CAS  Google Scholar 

  3. Faulk P. W., Gerard J. P., Welscher H. D.: Cell mediated immunity to insulin and its polypeptide chains in insulin-treated diabetics — Int. Arch. Allergy48, 364, 1975.

    PubMed  CAS  Google Scholar 

  4. Ghambir K. K., Archer J. A., Bradley C. J.: Characteristics of human erythrocyte insulin receptors — Diabetes27, 701, 1978.

    Article  Google Scholar 

  5. Goldman J., Carpenter F. H.: Zinc binding circular dichroism and equilibrium. Sediment studies on insulin (bovine) and several of its derivations — Biochemistry (Wash.)13, 4566, 1974.

    CAS  Google Scholar 

  6. Julius M. H., Simpson E., Herzenberg L. A.: A rapid method for the isolation of functional thymus derived murine lymphocytes — Europ. J. Immunol.3, 649, 1973.

    Google Scholar 

  7. Kolb H., Keck K., Momayezi M., Schigker C., Trissi D.: Ir-gene control of antibody class production — J. Immunol.118, 427, 1977.

    PubMed  CAS  Google Scholar 

  8. Kontainen S.: Human insulin-specific suppressor factors. Induction, characteristics and comparison to murine factors — Clin. exp. Immunol.47, 715, 1982.

    Google Scholar 

  9. Krug U., Krug F., Cuatrecasas P.: Emergence of insulin receptors on human lymphocytes duringin vitro transformation — Proc. nat. Acad. Sci. (Wash.)69, 260–264, 1972.

    Article  Google Scholar 

  10. Kurtz A. B., Nabarro J. D. N.: Circulating anti-binding antibodies — Diabetologia19, 329, 1980.

    Article  PubMed  CAS  Google Scholar 

  11. Ledbetter J. A., Evans R. L., Lipinski M., Cunnincham-Rundles C., Good R. A., Herzenberg L. A.: Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and T cytotoxic/suppressor subpopulations in mouse and man — J. exp. Med.153, 310, 1981.

    Article  PubMed  CAS  Google Scholar 

  12. MacCuish A. C., Jordan C. J., Campbell C. J., Duncan L. J. P., Irvine W. J.: Cell mediated immunity in diabetes mellitus. Lymphocyte transformation by insulin and insulin fragments in insulin-treated and newly diagnosed diabetics — Diabetes24, 36, 1975.

    Article  PubMed  CAS  Google Scholar 

  13. Mann D. L., Mendell N., Kahn R. C., Johnson A. J., Rosenthal A.:In vitro lymphocyte proliferation response to therapeutic insulin components: evidence for genetic control by the human major histocompatibility complex — J. clin. Invest.72, 1130, 1983.

    Article  PubMed  CAS  Google Scholar 

  14. Nell L. J., Thomas J. W.: The human immune response to insulin. Kinetic and cellular aspects of the lymphocyte proliferative response in diabetes — J. Immunol.131, 701, 1983.

    PubMed  CAS  Google Scholar 

  15. Rosenthal A. S., Barcinski M. A., Blake J. T.: Determinant selection in a macrophage dependent immune response gene function — Nature (Lond.)267, 156, 1977.

    Article  CAS  Google Scholar 

  16. Scheiner T., Groop L., Nikkiln A., Kontiaineu S.: Proliferative responses to insulin antigens in diabetes and controls — J. clin. Lab. Immunol.11, 135, 1983.

    Google Scholar 

  17. Splenar I., Neri T. M., Berger W., Erb P.: Association of specific immune response to pork and beef insulin with certain HLA-DR antigens in Type 1 diabetes — Brit. med. J.285, 1451, 1982.

    Article  Google Scholar 

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Author notes

  1. Elizabeth R. Richens

    Present address: Department of Microbiology Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait

Authors and Affiliations

  1. Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Bath

    Elizabeth R. Richens, Mary E. Seward & Robert W. Groves

Authors
  1. Elizabeth R. Richens
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  2. Mary E. Seward
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  3. Robert W. Groves
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This work was funded by a grant from the Wellcome Foundation.

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Richens, E.R., Seward, M.E. & Groves, R.W. Cellular cytotoxicity to membrane-associated insulin in an autologous system. Acta diabet. lat 22, 55–62 (1985). https://doi.org/10.1007/BF02591093

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  • DOI: https://doi.org/10.1007/BF02591093

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