Summary
The IL-2 system which involves IL-2 production, IL-2 receptor expression, and response to IL-2, is associated with autoimmune phenomena. Immunologi-cal abnormalities including autoimmune phenomena are believed to contribute to the pathogenesis of IDDM. In this study, the production of IL-2, the responses to IL-2 and IL-2 receptor expression by peripheral blood T lymphocytes were compared in IDDM and normal non-diabetic children. The percentage of IL-2 receptor-positive circulating T cells was significantly increased in diabetic children, although IL-2 receptor expression induced by con A stimulation did not differ in the diabetic and control children. IL-2 production was significantly decreased in diabetic children compared with the control children. The response of stimulated T cells to IL-2 did not differ in IDDM and control children. In IDDM, IL-2 production by CD4-positive T lymphocytes within the IL-2 system is thought to be selectively defective. On the other hand, IL-4, which is also produced by CD4-positive T lymphocytes, was increased. Since IL-4 did not suppress IL-2 production, it would seem that the IL-2 producing subset in CD4+HLA-DR+ T cells is decreased in IDDM. These results suggest that in recent onset IDDM, IL-2 receptor-positive circulating T cells require an IL-2 supply.[Diabetologia (1994) 37: 476-482]
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Abbreviations
- IDDM:
-
insulin-dependent diabetes mellitus
- IL:
-
interleukin
- con A:
-
concanavalin A
- PMNC:
-
peripheral mononuclear cells
- ICA:
-
islet cell antibody
References
Diabetes Epidemiology Research International Group (1988) Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes 37: 1113–1119
Diabetes Epidemiology Research International Group (1990) Secular trends in incidence of childhood IDDM in 10 countries. Diabetes 39: 858–864
Takeo J, Maeda H, Tokunaga K, Ishiba S, Maruyama H (1984) HLA in Japanese insulin-dependent diabetes mellitus. Acta Pediatr Jpn 26: 289–293
Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet-cell antibodies in diabetes mellitus with autoimmune poly-endocrine deficiencies. Lancet II: 1279–1283
MacCuish AC, Bvarnes EW, Irvine WJ, Duncan UP (1974) Antibodies to pancreatic islet cells in insulin-dependent diabetics with coexistent autoimmune disease. Lancet II. 1529–1531
Eisenbarth GS (1986) Type I diabetes mellitus, A chronic autoimmune disease. N Engl J Med 314: 1360–1368
Bottazzo GF, Dean B, McNally J, Mckay E, Swift GF, Gamble D (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas diabetic insulitis. N Engl J Med 313: 353–360
Patkau V, Shaw J, Mills G, Caplan B (1980) Cellular origins and targets of costimulator (IL-2). Immunol Rev 51: 157–175
Palacios R, Moller G (1981) Cell growth factor abrogates concanavalin-A induced suppresser cell function. J Exp Med 153: 1360–1365
Kern D, Gillis S, Okada M, Henney C (1981) The role of in-terleukin-2 (IL-2) in the differentiation of cytotoxic T cells: the effect of monoclonal anti-IL-2 antibody and absorption with IL-2-dependent T cell lines. J Immunol 127: 1323–1328
Zier KS, Leo MM, Spielman RS, Baker L (1984) Decreased synthesis of interleukin-2 (IL-2) in insulin-dependent diabetes mellitus. Diabetes 33: 552–555
Kaye WA, Adri MNS, Soeldner JSI et al. (1986) Acquired defect in interleukin-2 production in patients with type I diabetes mellitus. N Engl J Med 315: 920–924
Gillis S, Ferm MM, Ou W, Smith K (1978) T cell growth factor: parameters of production and quantitative microassay for activity. J Immunol 120: 2027–2032
Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: laboratory manual. Cold Spring Harbor Laboratory, New York, pp 196–202
Davies LG, Dibner MD, Battey JF (1986) Basic methods in molecular biology. Elsevier, New York, pp 143–146
Taniguchi T, Matsui H, Fujita T et al. (1983) Structure and expression of a cloned cDNA for human interleukin-2. Nature 302: 305–309
Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T (1985) Molecular structure of the human cytoplasmic B-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci USA 82: 6133–6138
Taniguchi T, Yamaguchi K, Yamamoto T et al. (1988) Depression in gene expression for poly (ADP-ribose) synthe-tase during the interferon-induced activation process of murine macrophage tumor cells. Eur J Biochem 171: 571–575
Watson JL, Aarden JS, Paetkan V (1979) Molecular and quantitative analysis of helper T cell-replacing factors on the induction of antigen-sensitive B and T lymphocytes. J Immunol 122: 1633–1638
Varela JA, Segovia DA (1981) Decrease production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus. J Clin Invest 69: 1388–1392
Altman A, Theofilopoulos AN, Weiner R, Katg D, Dexon F (1981) Analysis of Tcell function in autoimmune murine strains. J Exp Med 154: 791–808
Wofsy D, Murphy ED, Roths JB, Dauphinee MJ, Kipper SB, Talal N (1981) Deficient interleukin 2 activity in MRL-Mp and C57BL/6J mice bearing the 1 pr gene. J Exp Med 154: 1671–1680
Serreze DV, Leiter EH (1987) Defective activation of T suppressor cell function in nonobese diabetic mice. J Immunol 140: 3801–3807
Cavallo MG, Signore A, Baroni MG, Andreani D, Pozzilli P (1989) Interleukin 2 (IL2) production and IL2 receptor release in type I diabetes mellitus. Diabetes Nutr Metab 2: 179–183
Lorini R, Montagna D, Lanfranchi A et al. (1989) Alteration of in vitro interleukin 1 and 2 in diabetic children. Eur J Pedi-atr 148: 732–736
Mossmann TR, Cherwinski H, Bond MW, Giodlin MA, Coffman RL (1986) Two type of murine helper T cells. 1. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136: 2348–2354
Kim J, Woods A, Becker-Dunn E, Bottomly K (1985) Distinct functional phenotypes of cloned la-restricted helper T cells. J Exp Med 162: 188–193
Boom WH, Liano D, Abbas K (1988) Heterogeneity of hel-per/inducer T lymphocytes. II. Effect of interleukin-4 and in-terleukin-2 producing T cell clones on resting B cells. J Exp Med 167: 1350–1357
Gaya A, Calle ODL, Yague J et al. (1991) IL-4 inhibits IL-2 synthesis and IL-2-induced up-regulation of IL-2Ra but not IL-2RB chain in CD4+ human T cells. J Immunol 146: 4209–4214
Rapoport MJ, Jaramillo A, Zipris D et al. (1993) Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. J Exp Med 178: 87–99
Zielasek J, Burkart V, Naylor P, Goldstein A, Kiesel U, Kolb H (1990) Interleukin 2-dependent control of disease development in spontaneously diabetic BB rats. Immunology 69: 209–214
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Tomoda, T., Kurashige, T. & Taniguchi, T. Imbalance of the interleukin 2 system in children with IDDM. Diabetologia 37, 476–482 (1994). https://doi.org/10.1007/s001250050135
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DOI: https://doi.org/10.1007/s001250050135