Lymphocyte Response in Diabetes Mellitus

  • Sudhir Gupta


During the past decade evidence has accumulated to suggest that the immune system plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (Type I), which appears to be pathogenically a distinct disorder from insulin-independent diabetes (Type II). Studies in experimental animals have further suggested the role of lymphocytes and their subsets in the pathogenesis of Type I diabetes. It would be appropriate to discuss lymphocytes in general before discussing lymphocytes in diabetes mellitus.


Insulin Receptor Migration Inhibition Factor Lymphocyte Subpopulation Lymphocyte Response Islet Cell Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abo, T., and Balch, C. M., 1981, A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK1) J. Immunol. 127: 1024–1029.PubMedGoogle Scholar
  2. Bersani, G., Zanco, P., Padovan, D., and Betterle, C., 1981, Lymphocyte subpopulations in insulindependent diabetics with or without serum islet-cell autoantibodies, Diabetologia 20: 47–50.PubMedCrossRefGoogle Scholar
  3. Boitard, C., Debray-Sachs, M., Pouplard, A., Assan, R., and Hamburger, J., 1981, Lymphocytes from diabetics suppress insulin release in vitro, Diabetologia 21: 41–46.PubMedCrossRefGoogle Scholar
  4. Brody, J. I., and Merlie, K., 1970, Metabolic and biosynthetic features of lymphocytes from patients with diabetes mellitus: Similarities to lymphocytes in chronic lymphocytic leukemia, Br. J. Haematol. 19: 193–201.PubMedCrossRefGoogle Scholar
  5. Buschard, K., Madsbad, S., and Rygaard, J., 1980, Depressed suppressor cell activity in patients with newly diagnosed insulin-dependent diabetes mellitus, Clin. Exp. Immunol. 41: 25–32.PubMedGoogle Scholar
  6. Buschard, K., Madsbad, S., Krarup, T., and Rygaard, J., 1982, Glycaemic control and suppressor cell activity in patients with insulin-dependent diabetes mellitus, Clin. Exp. Immunol. 48: 189–195.PubMedGoogle Scholar
  7. Cattaneo, R., Saibene, V., and Pozza, G., 1976, Peripheral T-lymphocytes in juvenile-onset diabetics (JOD) and in maturity-onset diabetics (MOD), Diabetes 25: 223–226.PubMedCrossRefGoogle Scholar
  8. Damle, N. K., Hansen, J. A., Good, R. A., and Gupta, S., 1981, Monoclonal antibody analysis of human T lymphocyte subpopulations exhibiting autologous mixed lymphocyte reaction, Proc. Natl. Acad. Sci. (USA) 78: 5096–5099.CrossRefGoogle Scholar
  9. Damle, N. K., and Gupta, S., 1982, Autologous mixed lymphocyte reaction in man. V. Functionally and phenotypically distinct human T-cell subpopulations responding to non-T and activated T cells in AMLR, Scand. J. Immunol. 16: 59–68.PubMedCrossRefGoogle Scholar
  10. Delepesse, J., Duchateau, J., Bastenie, P. A., Lauvaux, J. P., Collet, H., and Govaerts, A., 1974, Cell-mediated immunity in diabetes mellitus, Clin. Exp. Immunol. 18: 461–467.Google Scholar
  11. Dolkart, R. E., Halpern, B., and Perlman, J., 1971, Comparison and antibody responses in normal and alloxan diabetic mice, Diabetes 20: 162–167.Google Scholar
  12. Fabris, N., and Piantanelli, L., 1977, Differential effect of pancreatectomy on humoral and cell-mediated immune response, Clin. Exp. Immunol. 28: 315–325.PubMedGoogle Scholar
  13. Fairchild, R. S., Kyner, J. L., and Abdon, N. I., 1982, Specific immunoregulation abnormality in insulin dependent diabetes mellitus, J. Lab. Clin. Med. 99: 175–185.PubMedGoogle Scholar
  14. Farid, N. R., and Anderson, J., 1973, Immunoglobulins and complement in diabetes mellitus, Lancet 2: 92.PubMedCrossRefGoogle Scholar
  15. Faulk, W. P., Girard, J. P., and Welscher, H. D., 1975, Cell-mediated immunity to insulin and its polypeptide chains in insulin-treated diabetics, Int. Arch. Allergy Appl. Immunol. 48: 364–371.PubMedCrossRefGoogle Scholar
  16. Gavin, J. R., Roth, J., Jen, P., and Freychet, P., 1972, Insulin receptors in human circulating cells and fibroblasts, Proc. Natl. Acad. Sci. (USA) 69: 747–751.CrossRefGoogle Scholar
  17. Gelfand, E. W., Ipp, M. M., and Riordan, J. R., 1982, Insulin modulation of antibody-dependent cytotoxicity and the detection of anti-receptor antibodies, J. Lab. Clin. Med. 99: 39–45.PubMedGoogle Scholar
  18. Gepts, W., 1965, Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14: 619–633.PubMedGoogle Scholar
  19. Glassman, A. B., and Bennett, C. E., 1980, B and T lymphocytes: Quantitation, Function, and clinical applicability, Ann. Clin. Lab. Sci. 8: 455–462.Google Scholar
  20. Gozes, Y., Carusso, J., and Strom, T. B., 1981, The absence of cryptic insulin receptors on resting lymphocytes, Diabetes 30: 314–316.PubMedCrossRefGoogle Scholar
  21. Gupta, S., 1978, Functionally distinct subpopulations of human T lymphocytes. A brief review, Clin, Bull. 8: 100–107.Google Scholar
  22. Gupta, S., 1981, Human T cell subpopulations with receptors for immunoglobulin isotypes, Clin. Immunol. Newsletter 2: 51–57.CrossRefGoogle Scholar
  23. Gupta, S., and Good, R. A., 1978, Human T cell subsets in health and disease, in: Human Lymphocyte Differentiation: Its Application to Cancer ( B. Serrou and S. Rosenfeld, eds.), pp. 367–374, North-Holland Biomedical Press, Amsterdam.Google Scholar
  24. Gupta, S., and Good, R. A., 1979b, Lymphocytes-1979, Henry Ford Hosp. Med. J. 27: 224–235.Google Scholar
  25. Gupta, S., and Good, R. A., 1979a, Human T lymphocytes as defined by Fc receptors, Thymus 1: 135–149.PubMedGoogle Scholar
  26. Gupta, S., and Good, R. A., 1980, Markers of human lymphocyte subpopulations in primary immunodeficiency and lymphoproliferative disorders, Semin. Hematol. 17: 1–29.PubMedGoogle Scholar
  27. Gupta, S., and Good, R. A., 1981a, Subpopulations of human T lymphocytes. Laboratory and clinical studies, Immunol. Rev. 56: 89–114.PubMedCrossRefGoogle Scholar
  28. Gupta, S., and Good, R. A., 1981b, Clinical significance of human lymphocyte subpopulations, in: Contemporary Hematology ( A. S. Gordon, R. D. Silber, and J. LoBue, eds.), pp. 153–226, Plenum Press, New York.Google Scholar
  29. Gupta, S., and Kapoor, N., 1980, Lymphocyte subpopulations; surface, intracellular, enzymatic markers and functions, in: Infections Complicating the Abnormal Host ( M. H. Grieco, ed.), pp. 84–128, Yorke Medical Books, New York.Google Scholar
  30. Gupta, S., Winchester, R. J., and Good, R. A., 1980a, General orientation of human lymphocyte subpopulations, in: Clinical Immunobiology, vol. 4 (F. H. Bach and R. A. Good, eds)., pp. 1–31 Academic Press, New York.Google Scholar
  31. Gupta, S., Fernandes, G., Rocklin, R., and Good, R. A., 1980, Histamine receptors on human T cell subsets, in: International Symposium on New Trends in Human Immunology and Cancer Immunology ( B. Serrou and C. Rosenfeld, eds.), pp. 36–47, Doin Editier, Paris.Google Scholar
  32. Gupta, S., Fikrig, S. M., Damle, N. K., Khanna, S., and Orti, E., 1981, Abnormal immunoregulatory function in patients with insulin-dependent diabetes mellitus, Human Lymphocyte Differentiation 1: 197–202.Google Scholar
  33. Gupta, S., Fikrig, S. M., Khanna, S., and Orti, E., 1982, Deficiency of suppressor T cells in insulin- dependent diabetes mellitus. An analysis with monoclonal antibodies, Immunol. Lett. 4: 289–294.PubMedCrossRefGoogle Scholar
  34. Gupta, S., Fikrig, S., and Orti, E., 1983, Autologous mixed lymphocyte reaction in man. VI. Deficiency of autologous mixed lymphocyte reaction in type I (insulin-dependent) diabetes mellitus, J. Lab. Clin. Med. 11: 59–62.Google Scholar
  35. Hann, S., Kaye, R., and Falkner, B., 1976, Subpopulations of peripheral lymphocytes in juvenile diabetes, Diabetes 25: 101–103.PubMedCrossRefGoogle Scholar
  36. Helderman, J. H., 1981, Role of insulin in the intermediary metabolism of the activated thymic-derived lymphocyte, J. Clin. Invest. 67: 1636–1642.PubMedCrossRefGoogle Scholar
  37. Helderman, J. H., and Raskin, P., 1980, The T lymphocyte insulin receptor in diabetes and obesity. An intrinsic binding defect, Diabetes 29: 551–557.PubMedGoogle Scholar
  38. Helderman, J. H., and Strom, T. B., 1978, Specific insulin binding site on T and B lymphocytes as a marker of cell activation, Nature 274: 62–63.PubMedCrossRefGoogle Scholar
  39. Helderman, J. H., Strom, T. B., and Dupuy-D’Angeac, A., 1979, A close relationship between cytotoxic T lymphocytes generated in the mixed lymphocyte culture and insulin-receptor bearing lymphocytes. Enrichment by density gradient centrifugation, Cell Immunol. 46: 247–258.PubMedCrossRefGoogle Scholar
  40. Horowitz, S. D., Borcherding, W., and Bargman, G. J., 1977, Suppressor T cell function in diabetes mellitus, Lancet 2: 1291.PubMedCrossRefGoogle Scholar
  41. Huang, S-W., and MacLaren, N. K.,1976, Insulin-dependent diabetes: A disease of autoaggression, Science 193: 64–66.Google Scholar
  42. Jackson, R. A., Morris, M. A., Haynes, B. F., and Eisenbarth, G. S., 1982,1 Increased circulating Iaantigen-bearing T cells in type I diabetes mellitus, N. Engl. J. Med. 306: 785–788.Google Scholar
  43. Krug, U., Krug, F., and Cuatrecasas, P., 1972, Emergence of insulin receptors on human lymphocytes during in vitro transformation, Proc. Natl. Acad. Sci. (USA) 69: 2604–2608.CrossRefGoogle Scholar
  44. Lederman, M. M., Ellner, J., and Rodman, H. M., 1981, Defective suppressor cell generation in juvenile onset diabetes, J. Immunol. 127: 2051–2055.PubMedGoogle Scholar
  45. Lipscomb, H., Dodson, H. L., and Green, J. A., 1959, Infection in the diabetic. South Med. J. 52: 16–23.PubMedCrossRefGoogle Scholar
  46. Ludwig, H., Erbl, M., Schemthaner, G., Erd, W., and Maye, W. R., 1976, Humoral immunodeficiency to bacterial antigens in patients with juvenile onset diabetes mellitus, Diabetologia 12: 259–262.PubMedCrossRefGoogle Scholar
  47. MacCuish, A. C., Jordan, J., Campbell, C. J., Duncan, L. P. J., and Irvine, W. J., 1974a, Cell-mediated immunity to immunity to human pancreas in diabetes mellitus, Diabetes 23: 693–697.PubMedGoogle Scholar
  48. MacCuish, A. C., Urbaniak, S. J., Campbell, C. J., Duncan, L. P. J., and Irvine, W. J., 1974b, Physohemagglutinin transformation and circulating lymphocyte subpopulations in insulin-dependent diabetic patients, Diabetes 23: 708–712.PubMedGoogle Scholar
  49. MacCuish, A. C., Jordan, J., Campbell, C. J., Duncan, L. P. J., and Irvine, W., J., 1975, Cell-mediated immunity in diabetes mellitus. Lymphocyte transformation by insulin and insulin fragments in insulin-treated and newly-diagnosed diabetics, Diabetes 24: 36–43.PubMedCrossRefGoogle Scholar
  50. Mascart-Lemone, F., Delespesse, G., Dorchy, H., Lemiere, B., and Servais, G., 1982, Characterization of immunoregulatory T lymphocytes in insulin-dependent diabetic children by means of monoclonal antibodies, Clin. Exp. Immunol. 47: 296–300.PubMedGoogle Scholar
  51. Moretta, L., Ferrarini, M., and Cooper, M. D., 1978, Characterization of human T cell subpopulations as defined by specific receptors for immunoglobulins, Contemp. Top. Immunobiol., 8: 19–53.PubMedCrossRefGoogle Scholar
  52. Nadler, L. M., Stashenko, P., Hardy, R., van Agthoven, A., Terhorst, C., and Schlossman, S. F., 1981a, Characterization of a human B cell-specific antigen (B2) distinct from B l, J. Immunol. 126: 1941–1947.PubMedGoogle Scholar
  53. Nadler, L. M., Ritz, J., Hardy, R., Pesando, J. M., and Schlossman, S. F., 1981b, A unique cell surface antigen identifying lymphoid malignancies of C cell origin, J. Clin. Invest. 67: 134–140.PubMedCrossRefGoogle Scholar
  54. Nerup, J., Andersen, O. O., Bendixen, G., Egeberg, J., and Poulsen, J. E., 1971, Antipancreatic cellular hypersensitivity in diabetes mellitus, Diabetes 20: 424–427.PubMedGoogle Scholar
  55. Nerup, J., Andersen, O. O., Bendixen, G., Egeberg, J., Gunnarsson, R., Kromann, H., and Poulsen, J. E., 1974, Cell-mediated immunity in diabetes mellitus, Proc. R. Soc. Med. 67: 506–513.PubMedGoogle Scholar
  56. Nieminen, P., Paasivuo, R., and Saksela, E., 1982, Effect of a monoclonal anti-large granular lymphocyte antibody on the human NK activity, J. Immunol. 128: 1097–1101.PubMedGoogle Scholar
  57. Ortaldo, J. R., Sharrow, S. O., Timonen, T., and Herberman, R. B., 1981, Determination of surface antigens on highly purified NK cells by flow cytometry with monoclonal antibodies, J. Immunol. 127: 2401–2409.PubMedGoogle Scholar
  58. Pozzilli, P., Sensi, M., Gorsuch, A., Bottazzo, G. F., and Cudworth, A. G., 1979, Evidence for raised K-cell levels in type I diabetes, Lancet 2: 173–175.PubMedCrossRefGoogle Scholar
  59. Ragab, A. H., Hazlett, B., and Cowan, D. H., 1972, Response of peripheral blood lymphocytes from patients with diabetes mellitus to phytohemaggutinin and candida albicans antigen, Diabetes 21: 906–907.PubMedGoogle Scholar
  60. Reinherz, E. L., and Schlossman, S. F., 1980, The differentiation and function of human T lymphocytes, Cell 19: 821–827.PubMedCrossRefGoogle Scholar
  61. Reinherz, E. L., Moretta, L., Roper, M., Breard, J. M., Mingari, M. C., Cooper, M. D., and Schlossman, S. F., 1980, Human T lymphocyte subpopulations defined by Fc receptors and monoclonal antibodies. A comparison, J. Exp. Med. 151: 969–976.PubMedCrossRefGoogle Scholar
  62. Reinherz, E. L., Morimoto, C., Fitzgerald, K. A., Hussey, R. E., Daley, J. F., and Schlossman, S. F., 1982, Heterogeneity of human OKT4 + cells defined by a monoclonal antibody that delineates two functional subpopulations, J. Immunol. 128: 463–468.PubMedGoogle Scholar
  63. Richens, E. R., Ancill, R. J., Gough, K. R., and Harbog, M., 1973, Cellular hypersensitivity to mitochondrial antigens in diabetes mellitus, Clin. Exp. Immunol. 13: 1–7.PubMedGoogle Scholar
  64. Rocklin, R. E., Beard, J., Gupta, S., Good, R. A., and Melman, K., 1979, Characterization of the human blood lymphocytes that produce a histamine-induced suppressor factor (HSF), Cell Immunol. 51: 226–237.CrossRefGoogle Scholar
  65. Ross, G. D., 1979, Identification of human lymphocyte subpopulations by surface marker analysis, Blood 53: 799–811.PubMedGoogle Scholar
  66. Schwartz, R. H., Bianco, A. R., Handbuerger, B. S., and Kahn, R., 1975, Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparation of human peripheral blood mononuclear leukocytes: Implications for studies of insulin-resistant states in man, Proc. Natl. Acad. Sci. (USA) 72: 474–478.CrossRefGoogle Scholar
  67. Selam, J. L., Clot, J., Andary, M., and Mirouze, J., 1979, Circulating lymphocyte subpopulations in juvenile insulin-dependent diabetes, Diabetologia 16: 35–40.PubMedCrossRefGoogle Scholar
  68. Sensi, M., Pozzilli, P., Gorsuch, A. N., Bottazo, G. F., and Cudworth, A. G., 1981, Increased killer cell activity in insulin-dependent (type I) diabetes mellitus, Diabetologia 20: 106–109.PubMedCrossRefGoogle Scholar
  69. Slater, L. M., Murray, S. L., Kershnar, A., and Mosher, M. A., 1980, Immunological suppressor cell activity in insulin-dependent diabetes, J. Clin. Lab. Immunol. 3: 105–109.PubMedGoogle Scholar
  70. Smith, W. I., Rabin, B. S., Huellmantel, A., Thiel, D. H. V., and Drash, A., 1978, Immunopathology of juvenile-onset diabetes mellitus. I. IgA deficiency and juvenile diabetes, Diabetes 27: 1092–1097.PubMedCrossRefGoogle Scholar
  71. Souadjian, J. V., Molnar, G. D., Silverstein, M. N., and Titus, J. L., 1970, Morphologic studies of the thymus in acromegaly, diabetes mellitus and Cushing’s syndrome, Metabolism 19: 401–405.PubMedCrossRefGoogle Scholar
  72. Stratton, J. A., Nies, K. M., Louie, J. S., and Sperling, M. A., 1970, Cellular immunity in juvenile diabetes mellitus, Diabetes 15: 101.Google Scholar
  73. Strom, T. B., Bear, R. A., and Carpenter, C. B., 1975, Insulin-induced augmentation of lymphocyte-mediated cytotoxicity, Science 187: 1206–1208.PubMedCrossRefGoogle Scholar
  74. Thomas, Y., Rogozinski, L., Irigoyen, O. H., Shen, H. H., Talle, M. A., Goldstein, G., and Chess, L., 1982, Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4 + population belong to a distinct subset, J. Immunol. 128: 1386–1390.PubMedGoogle Scholar
  75. Timonen, T., Ranki, A., Saskela, E., and Hayry, P., 1979, Fractionation, morphological and functional characterization of effector cells responsible for human natural killer activity against cell-line targets, Cell Immunol. 48: 121–132.PubMedCrossRefGoogle Scholar
  76. Uchiama, T., Nelson, D. L., Fleisher, T. A., and Waldmann, T. A., 198la, A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells and one of two types of helper T cells, J. Immunol. 126: 1398–1403.Google Scholar
  77. Uchiama, T., Broder, S., and Waldman, T. A., 1981b, A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells, J. Immunol. 126: 1393–1397.Google Scholar
  78. Zola, H., 1980, Monoclonal antibodies against human cell membrane antigen. A review, Pathology 12: 539.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Sudhir Gupta
    • 1
  1. 1.Division of Basic and Clinical Immunology, Department of MedicineUniversity of California, IrvineIrvineUSA

Personalised recommendations