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Prospective study of lymphocyte subsets in subjects genetically susceptible to Type 1 (insulin-dependent) diabetes

Summary

A prospective study of lymphocyte subsets has been carried out for 18 months in 58 healthy first-degree relatives of Type 1 (insulin-dependent) probands. Subjects selected for presence or absence of islet cell antibodies included 10 with complement-fixing islet cell antibodies, 10 with conventional islet cell antibodies and 38 without islet cell antibodies. Immunoregulatory and effector lymphocyte subsets, and in particular activated T-cells, were investigated using a panel of monoclonal antibodies. The results showed no significant changes in total T, helper, suppressor/cytotoxic cells or K/ NK cells. Activated T-cells were observed at least once in 22 subjects using the 4F2 monoclonal antibody and in 11 using the Tac antibody. Seven subjects had 4F2-positive cells on repeated occasions and one twice showed Tac-positive cells. Fluctuations and/or loss of islet cell antibodies were observed during follow-up. There was no correlation between presence of activated T-cells and either islet cell antibody status or HLA haplotype sharing with the diabetic proband. On the other hand, a significant correlation was observed between HLA-DR3 positivity of subjects and the occurrence of activated T-cells (both 4F2-positive and Tac-positive). We conclude that subjects with HLA-DR3 may be especially prone to T-cell activation. As none of the ‘high risk’ individuals developed diabetes in the course of follow-up, the relevance of these observations in the pathogenesis of Type 1 diabetes needs more prolonged investigation.

References

  1. Jackson RA, Morris MA, Haynes BF, Eisenbarth GS (1982) Increased circulating Ia bearing T cells in Type 1 diabetes mellitus. N Engl J Med 306: 785–788

    Google Scholar 

  2. Pozzilli P, Zuccarini O, Iavicoli M, Andreani D, Spencer KM, Bottazzo GF, Beverley PCL, Kyner JL, Cudworth AG (1983) Monoclonal antibodies defined abnormalities of T lymphocytes in Type 1 diabetes. Diabetes 32: 91–94

    Google Scholar 

  3. Buschard K, Madsbad S, Rygaard J (1980) Depressed suppressor cell activity in patients with newly diagnosed insulin dependent diabetes mellitus. Clin Exp Immunol 45: 25–31

    Google Scholar 

  4. Fairchild RS, Kyner JL, Abdou NI (1982) Specific immunoregulation abnormality in insulin dependent diabetes mellitus. J Lab Clin Med 99: 175–186

    Google Scholar 

  5. Pozzilli P, Sensi M, Gorsuch AN, Bottazzo GF, Cudworth AG (1979) Evidence for raised K cell levels in Type 1 diabetes. Lancet 2: 173–175

    Google Scholar 

  6. Sensi M, Pozzilli P, Gorsuch AN, Bottazzo GF, Cudworth AG (1981) Increased killer cell activity in Type 1 diabetes. Diabetologia 20: 106–109

    Google Scholar 

  7. Bottazzo GF, Pozzilli P, Mirakian R, Dean BM, Doniach D (1984) Early immunological events in diabetes. In: Andreani D, Di Mario U, Federlin KF, Heding LG (eds) Immunology in diabetes. Kimptom Medical Publications, London, pp95–104

    Google Scholar 

  8. Cudworth AG, Wolf E (1982) The genetic susceptibility to Type 1 diabetes. Clin Endocrinol Metab 11: 389–406

    Google Scholar 

  9. Wolf E, Spencer KM, Cudworth AG (1983) The genetic susceptibility to Type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association. Diabetologia 24: 224–230

    Google Scholar 

  10. Beverley PCL, Callard RE (1981) Distinctive functional characteristics of lymphocytes defined by E-rosetting or a monoclonal antibody anti-T cell antibody. Eur J Immunol 11: 329–334

    Google Scholar 

  11. Beverley PCL (1982) The application of monoclonal antibodies to the study of lymphoreticular cells. Proc Roy Soc Edinburgh 13: 521–527

    Google Scholar 

  12. Bay Y, Callard RE, Beverley PCL, Bodmer WF (1983) Two monoclonal antibodies (H25 and H366) defined cells with K/NK activity. Eur J Immunol 48: 189–195

    Google Scholar 

  13. Haynes BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer JH, Mostowski HS, Thomas CA, Strominger JL, Fauci AS (1980) Characterisation of a monoclonal antibody (4F2) which binds to human monocytes and to a subset of activated lymphocytes. J Immunol 126: 1409–1411

    Google Scholar 

  14. Leonard JJM, Depper T, Uchiyama T, Smith KA, Waldmann TA, Greene C (1982) A monoclonal antibody that appears to recognize the receptor for human T cell growth factor: partial characterization of the receptor. Nature (Lond) 300: 267–269

    Google Scholar 

  15. Sensi M, Pozzilli P, Di Mario U (1984) A method to facilitate the reading of up to 60 samples of monoclonal antibody-fluorescence stained cells using Medicell HLA-DR plates. J Clin Lab Immunol 13:101–102

    Google Scholar 

  16. Bottazzo GF, Dean BM, Gorsuch AN, Cudworth AG, Doniach D (1980) Complement fixing islet cell antibodies in Type 1 diabetes: possible monitors of active beta cell damage. Lancet 1: 668–672

    Google Scholar 

  17. Bodmer WF (1980) The HLA system and disease. J Roy Coll Physicians 14: 43–50

    Google Scholar 

  18. Bodmer WF (1981) MHC gene clusters of man and mouse. In: Russell E (ed) Mammalian genetics and cancer, Alan Liss, New York, pp 213–240

    Google Scholar 

  19. Bottazzo GF, Pujol Borrell R, Hanafusa T (1983) Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2: 1115–1118

    Google Scholar 

  20. Lawley TJR, Hall A, Fauci AS, Katz SI, Hamburger MI, Frank MM (1981) Defective Fc receptor functions associated with the HLA-B8/DRW3 haplotype. N Engl J Med 304: 185–187

    Google Scholar 

  21. Spencer KM, Tarn A, Dean BM, Lister J, Bottazzo GF (1984) Family studies in Type 1 diabetes: evidence of fluctuating islet cell autoimmunity in unaffected relatives. Lancet 1: 764–765

    Google Scholar 

  22. Lamb JR, Feldmann M (1982) A human suppressor T cell clone which recognizes an autologous helper T cell clone. Nature 300: 456–458

    Google Scholar 

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Pozzilli, P., Sensi, M., Al-Sakkaf, L. et al. Prospective study of lymphocyte subsets in subjects genetically susceptible to Type 1 (insulin-dependent) diabetes. Diabetologia 27, 132–135 (1984). https://doi.org/10.1007/BF00275670

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  • DOI: https://doi.org/10.1007/BF00275670

Key words

  • Type 1 diabetes
  • pre-diabetic state
  • genetic susceptibility
  • lymphocyte subpopulations
  • activated T-cells