Summary
Peripheral blood lymphocytes have been investigated in 20 newly diagnosed type-I diabetics and 10 healthy subjects using monoclonal antibodies. Mononuclear cells were marked with anti-T-lymphocytes (Leu2, 3, 4, 12) and anti-Ia-antibodies (K14, L243) using indirect immunofluorescence. The percentage of circulating K14- and L243-positive cells was significantly higher in all diabetics than in normal controls. An increase in the number of K14-bearing cells was found in newly diagnosed patients with duration of less than 7 days (n=10) compared with diabetics of longer duration (1 to 8 months;n=10). Using dual-color immunofluorescence with fluorescein-conjugated anti-T-lymphocytes and rhodamin-conjugated anti-Ia-antibodies it was not possible to identify Ia-antigen bearing cells (Ia cells) as helper or suppressor lymphocytes. In addition, there was no significant difference in the number of Ia cells in diabetics with and without islet cell antibodies. It is concluded that there is evidence of activation of cellular immune response in type I diabetes, particularly in the early days of manifestation. However, previous assumptions that Ia cells represent T-cell activation have to be questioned.
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Abbreviations
- IDDM:
-
Insulin-dependent diabetes mellitus
- Ia-antigen:
-
Immune-response associated antigen
- ICA:
-
Islet cell antibodies
References
Alviggi L, Hoskins PJ, Pyke IA, Johnston C, Tee DEH, Leslie RDG (1984) Pathogenesis of insulin-dependent diabetes: a role for activated T-lymphocytes. Lancet 1:4
Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PGF, Gable DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetes insulin. N Engl J Med 313:353
Boyum A (1968) Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest 97:21
Burmester GR, Yu DTY, Ivani AM, Kunkel HG, Winchester RI (1981) Ia + T-cells in synovial fluid and tissues of patients with rheumatoid arthritis. Arthritis Rheum 24:1370
Buschard K, Röpke C, Madsbad S, Mehlsen J, Ruygaard J (1983) Lymphocyte subsets in patients with newly diagnosed type I diabetes: a prospective study. Diabetologia 25:247
Christy M, Deckert T, Nerup I (1977) Immunity and autoimmunity in diabetes mellitus. Clin Endocrinol Metab 6:305
Foulis AK, Steward JA (1984) The pancreas in recent-onset type I diabetes mellitus: insulin content of islets, insulitis and associated changes in exocrine acinar tissue. Diabetologia 26:456
Gepts W (1965) Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14:619
Herold KC, Huen A, Gould L, Traisman H, Rubenstein AH (1984) Alterations in lymphocyte subpopulations in type I diabetes mellitus: exploration of possible mechanisms and relationships to autoimmune phenomena. Diabetologia 27:102
Jackson R, Morris MA, Haynes BF, Eisenbarth GS (1982) Increased circulating Ia-antigen-bearing T-cells in type I diabetes mellitus. N Engl J Med 306:783
Johnson HE, Madsen M, Kristensen T, Kissmeyer-Nielsen F (1978) Expression of HLA-DR determinants on human T-cells in infectious mononucleosis. Scand J Immunol 8:160 (abstract)
Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature 256:495
Lernmark A (1985) Molecular biology of type I diabetes mellitus. Diabetologia 28:195
Lernmark A, Hägglof B, Freedman Z, Irvine J, Ludvigsson J, Holmgren G (1981) A prospective analysis of antibodies reacting with pancreatic islet cells in insulin dependent diabetic children. Diabetologia 20:471
Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis. A new model of diabetes mellitus. Science 193:415
Platz P, Jakobsen BK, Morling N, Nerup J et al. (1981) HLA-D- and DR-Antigens in genetic analysis of insulin dependent diabetes mellitus. Diabetologia 21:108
Pozzilli P, Zuccarini O, Lavicoli M, Andreani D, Spencer KM, Bottazzo GF, Cudworth G (1983) Monoclonal antibodies defined abnormalities of T-lymphocytes in type I diabetes. Diabetes 32:91
Pozzilli P, Sensi M, Al-Sakkaj L, Taru A, Zuccarini O, Bottazzo GF (1984) Prospective study of lymphocyte subsets in subjects genetically susceptible to type I diabetes. Diabetologia 27:132
Quinique-Debrie M, Debray-Sachs M, Dardenne M, Czeruichow P, Assan R, Bach JF (1985) Anti-islet cellular and humoral immunity, T-cell subsets, and thymic function in type I diabetes. Diabetes 34:373
Rodier M, Audary M, Richard JL, Mirouze J, Clot J (1984) Peripheral blood T-cell subsets studied by monoclonal antibodies in type I diabetes: effect of blood glucose control. Diabetologia 27:136
Schricker M (1983) Herstellung monoklonaler Antikörper gegen frühe Differenzierungsantigene auf Leukozyten. Inaugural dissertation, Munich
Volpe R (1984) Immunological aspects of thyroid disease. Triangle 23:95
Wolf E, Spencer KM, Cutworth AG (1983) The genetic susceptibility to type I diabetes: analysis of the HLA-DR association. Diabetologia 24:224
Yu DTY, Winchester RJ, Fu SM, Gibofsky A, Ko HS (1980) Peripheral blood Ia-positive T-cells. J Exp Med 151:91
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Ziegler, A.G., Standl, E., Lander, T. et al. Cell-Mediated autoimmunity at the onset of insulin-dependent diabetes mellitus (IDDM). Klin Wochenschr 65, 546–550 (1987). https://doi.org/10.1007/BF01727620
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DOI: https://doi.org/10.1007/BF01727620