Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-α in patients with recent-onset type 1 diabetes
Tóm tắt
Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-α and IL-1β, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes. We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry. T cell infiltration was less common in islets without beta cells (12.5 [0–33.3]%) than in those with beta cells (46.0 [17.4–83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-α was detected in 25.0 (4.3–46.9)% of macrophages and 11.8 (0–40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1β was detected in 1.8 (0–11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0–35.3)% of macrophages or 10.7 (0–31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]). Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-α and IL-1β) during the development of type 1A diabetes.
Tài liệu tham khảo
Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368
Hanafusa T, Miyazaki A, Miyagawa J et al (1990) Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 33:105–111
Thomas HE, Darwiche R, Corbett JA, Kay TW (1999) Evidence that beta cell death in nonobese diabetic mouse is Fas independent. J Immunol 163:1562–1569
Jiang Z, Woda BA (1991) Cytokine gene expression in the islets of the diabetic Biobreeding/Worcester rat. J Immunol 146:2990–2994
Iwahashi H, Hanafusa T, Eguchi Y et al (1996) Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2. Diabetologia 39:530–536
Corbett JA, Wang JL, Sweetland MA, Lancaster JR Jr, McDaniel ML (1992) Interleukin-1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. J Clin Invest 90:2384–2391
Yang XD, Tisch R, Singer SM et al (1994) Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. 1. The early development of autoimmunity and the diabetogenic process. J Exp Med 180:995–1004
Kagi D, Ho A, Odermatt B, Zakarian A, Ohashi PS, Mak TW (1999) TNF receptor 1-dependent beta cell toxicity as an effector pathway in autoimmune diabetes. J Immunol 162:4598–4605
Cailleau C, Diu-Hercend A, Ruuth E, Westwood R, Carnaud C (1997) Treatment with neutralizing antibodies specific for IL-1beta prevents cyclophosphamide-induced diabetes in nonobese diabetic mice. Diabetes 46:937–940
Thomas HE, Irawaty W, Darwiche R et al (2004) IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes 53:113–121
Sandberg JO, Eizirik DL, Sandler S (1997) IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice. Clin Exp Immunol 108:314–317
Yamagata K, Nakajima H, Tomita K et al (1996) Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 34:37–46
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 15:539–553
Imagawa A, Hanafusa T, Tamura S et al (2001) Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes 50:1269–1273
Itoh N, Hanafusa T, Miyazaki A et al (1993) Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest 92:2313–2322
Stassi G, Todaro M, Richiusa P et al (1995) Expression of apoptosis-inducing CD95 (Fas/Apo-1) on human beta-cells sorted by flow-cytometry and cultured in vitro. Transplant Proc 27:3271–3275
Moriwaki M, Itoh N, Miyagawa J et al (1999) Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset type 1 diabetes mellitus. Diabetologia 42:1332–1340
Calafiore R, Pietropaolo M, Basta G, Falorni A, Picchio ML, Brunetti P (1993) Pancreatic beta-cell destruction in non-obese diabetic mice. Metabolism 42:854–859
Nakayama M, Abiru N, Moriyama H et al (2005) Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 435:151–152
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252
Dahlen E, Dawe K, Ohlsson L, Hedlund G (1998) Dendritic cells and macrophages are the first and major producers of TNF-alpha in pancreatic islets in the nonobese diabetic mouse. J Immunol 160:3585–3593