Summary
Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset < 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4+: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8+: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1+: 11.5±3.8% versus 19.9±5.2%) (p< 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p< 0.01–0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p< 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Cahill GF, McDevitt HO (1981) Insulin-dependent diabetes mellitus: the initial lesion. N Engl J Med 304: 1454–1465
Buschard K, Madsbad S, Rygaard J (1980) Depressed suppressor cell activity in patients with newly diagnosed insulin-dependent diabetes mellitus. Clin Exp Immunol 41: 25–32
Galluzzo A, Giordano C, Sparacino G, Bompiani GD (1980) Studies on suppressor cell function in recent-onset juvenile diabetes. Diabetologia 19: 275 (Abstract)
Reinherz EL, Schlossman SF (1980) Current concepts in immunology. Regulation of the immune response-inducer and suppressor T lymphocyte subsets in human beings. N Engl J Med 303: 370–373
Reinherz EL, Kung PC, Breard JM, Goldstein G, Schlossman SF (1980) T cell requirements for generation of helper function in man: analysis of the subsets involved. J Immunol 124: 1883–1887
Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1980) A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol 124: 1301–1307
Bach MA, Bach JF (1981) The use of monoclonal anti-T cell antibodies to study T cell imbalances in human diseases. Clin Exp Immunol 45: 449–456
Cudworth AG, Woodrow JC (1976) Genetic susceptibility in diabetes mellitus. Br Med J 2: 846–848
Christy M, Green A, Christan B, Kromann H, Nerup J, Platz P, Thomsen M, Ryder L, Svejgaard A (1979) Studies of the HLA system and insulin-dependent diabetes mellitus. Diabetes Care 2: 209–214
National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057
Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scan J Clin Lab Invest 21: (Suppl 97): 77–89
Gorer PA, O'Gorman P (1956) The cytotoxic activity of isoantibodies in mice. Transplantation Bull 3:142–146
Bliss CI (1967) In: Statistics in biology, vol 1. McGraw-Hill, New York, pp 186–204
Welch BL (1947) Generalization of Student's t problem when several different population variances are involved. Biometrica 34: 28–35
Smolen JS, Chused TM, Leiserson WM, Reeves JP, Ailing D, Steimberg AD (1982) Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Am J Med 72: 783–790
Maclaren NK, Huang SW (1980) Cell-mediated immunity in insulin-dependent diabetes. In: Irvine WJ (ed) Immunology of diabetes. Teviot Scientific Publications, Edinburgh, pp 185–194
Pozzilli P, Zuccarini O, Iavicoli M, Andreani D, Sensi M, Spencer KM, Bottazzo GF, Beverley PCL, Kyner JL, Cudworth AG (1983) Monoclonal antibodies defined abnormalities of T lymphocytes in Type I (insulin-dependent) diabetes. Diabetes 32: 91–94
Jackson RA, Morris MA, Haynes BF, Eisenbarth GS (1982) Increased circulating la-antigen-bearing T cells in Type I diabetes mellitus. N Engl J Med 306: 785–788
Horita M, Suzuki H, Onodera T, Ginsberg-Fellner F, Fauci AS, Notkins AL (1982) Abnormalities of immunoregulatory T cell subsets in patients with insulin-dependent diabetes mellitus. J Immunol 129: 1426–1429
Gepts W, Le Compte PM (1981) The pancreatic islets in diabetes. Am J Med 70: 105–115
Kidd A, Okita N, Row VV, Volpé R (1980) The immunologic aspects of Graves' and Hashimoto's diseases. Metabolism 29: 80–84
Kaldany A, Hill T, Wentworth S, Brink SJ, D'Elia JA, Clouse M, Soedner JS (1982) Trapping of peripheral blood lymphocytes in the pancreas of patients with acute-onset insulin-dependent diabetes mellitus. Diabetes 31: 463–466
Gorsuch AN, Spencer KM, Lister J, McNally J, Dean BM, Bottazzo GF, Cudworth AG (1981) The natural history of Type I (insulin-dependent) diabetes mellitus: evidence for a long prediabetic period. Lancet 2: 1363–1365
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galluzzo, A., Giordano, C., Rubino, G. et al. Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26, 426–430 (1984). https://doi.org/10.1007/BF00262214
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00262214