Prevention of diabetes in nonobese diabetic mice by anti-I-A monoclonal antibodies: transfer of protection by splenic T cells.

Boîtard, Christian; Bendelac, Albert; Richard, M F; Carnaud, Claude; Bach, Jean‐François

doi:10.1073/pnas.85.24.9719

Cited by 111 publications

(47 citation statements)

References 43 publications

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“…Prior to all steps of the staining procedure, the cell surface and intracellular structures were saturated with PBS, 2% human serum and protein blocking reagent (Beckman Coulter, Unterschleissheim-Lohhof, Germany) for 30 min each. Single cells were indirectly stained for 30 min on ice for surface MHC class II expression with the monoclonal antibody 10.2-16 (reported to cross-react with I-A g7 [17]) (kindly provided by S. z. Lage) or the control antibody 14.4.4.S (anti-mouse I-E k , BD Biosciences, Heidelberg, Germany) which does not cross-react with NOD MHC class II ( [3] and own observations). After washing, cells were incubated with biotinylated R2-40 (anti-mouse IgG 2a/2b, BD Biosciences) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

et al. 2003

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Aims/hypothesis. In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A g7 expression in single pancreatic beta cells. Methods. Single-cell multiplex RT PCR and singlecell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. Results. Pancreatic beta cells from NOD mice express the I-A g7 protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed.

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Section: Methodsmentioning

confidence: 99%

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

et al. 2003

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“…A T-cell-mediated autoimmune pathogenesis is implicated because the disease can be passively transferred with lymphocytes into irradiated prediabetic mice (3) and prevented by treatment with antibodies directed against Thy-1.2 (4) and L3T4 (5) or by treatment with cyclosporin A (6). Diabetes can also be prevented by treatment with antibodies to class II Ia antigens (7). Untreated animals develop profound glucose intolerance and ketosis and die within weeks of the onset of overt diabetes.…”

mentioning

confidence: 99%

Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1.

Jacob

Aiso

Michie

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

308

171

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The role of tumor necrosis factor a (TNF-a) in the pathogenesis of autoimmune diabetes mellitus was tested in the nonobese mouse (NOD) model system. The effects of TNF-a were assessed on three levels: (i) insulitis development, (ii) development of overt diabetes, (iii) adoptive transfer of diabetes by splenic lymphocytes. Spontaneous diabetes mellitus was blocked in NOD mice by long-term treatment with recombinant TNF-a. Treatment with TNF-a caused'a significant reduction in the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Class II major histocompatibility complex Ia expression by islet cells was not up-regulated by TNF-a. Moreover, TNF-a was able to suppress the induction of diabetes in adoptive transfer of lymphocytes from diabetic female mice to young nondiabetic male NOD mice. These activities of TNF-a were shared by interleukin la in this system. These studies have implications for the pathogenesis and therapy of autoimmune diabetes mellitus.Nonobese diabetic (NOD) mice spontaneously develop diabetes remarkably similar to human autoimmune insulindependent diabetes mellitus. There is increasing evidence that the human and the NOD disease result from immune destruction of the insulin-producing beta cells in the islets of Langerhans (1). The disease is characterized by progressive lymphocyte infiltration into the islets (insulitis) prior to the expression of overt diabetes and by the appearance of anti-islet cell antibodies in the serum (2). A T-cell-mediated autoimmune pathogenesis is implicated because the disease can be passively transferred with lymphocytes into irradiated prediabetic mice (3) and prevented by treatment with antibodies directed against Thy-1.2 (4) and L3T4 (5) or by treatment with cyclosporin A (6). Diabetes can also be prevented by treatment with antibodies to class II Ia antigens (7). Untreated animals develop profound glucose intolerance and ketosis and die within weeks of the onset of overt diabetes. The role of lymphokines, especially interferon y (IFN-y), interleukin 1 (IL-1), and tumor necrosis factor a (TNF-a), in the pathogenesis of autoimmune diabetes has received increasing attention recently (8, 9). It was shown that IFN--y and TNF-a can induce the aberrant expression of class II major histocompatibility complex (MHC) molecules on pancreatic beta cells in vitro, suggesting a role for these lymphokines in the induction of the autoimmune process in diabetes (9). A different group of investigators has suggested that IL-1 is toxic to pancreatic beta cells in vitro and that TNF-a significantly enhances this toxicity (8). Recently we have suggested that TNF-a may play a significant role in preventing autoimmune nephritis in the (NZB3 x NZW)F1 lupus nephritis model system (10). Here we present evidence that TNF-a has a major effect in vivo by protecting NOD mice from developing autoimmune insulitis and diabetes. MATERIALS AND METHODSRecombinant murine TNF-a (0.53 mg/ml; 2.6 x 107 units/ml) was kindly provided by Genentech. Recom...

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“…The role of T cells in this model is shown by the predominance of T lymphocytes within the islet infiltrate (2,3), the preventive effect of neonatal thymectomy (4) and treatment with anti-CD4 (5) or anti-class II (6) monoslonal antibodies, and the induction of diabetes by transfer of T cells from diabetic NOD mice to nondiabetic B-cell-dOprived NOD recipients (7). Genetic studies have pointed to the role of major histocompatibility complex (MHC) genes in the susceptibility to diabetes (8,9).…”

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confidence: 99%

Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products.

Boîtard

Villà

Bécourt

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A- (20) were grown in RPMI 1640 medium supplemented with 10o fetal calf serum, 2 mM glutamine, penicillin at 100 units/ml, and streptomycin at 100 jg/ml (GIBCO/BRL). Normal islets were prepared by collagenase (Sigma) digestion of mouse pancreases as described by Lacy and Kotianovsky (21) with slight modifications (22).Western Blots. Cells (1 x 108) from each cell line were washed in Hanks' balanced saline solution, suspended in 7 ml of 0.01M Tris-buffered saline (TBS)/10 mM CaCl2/0.25 M sucrose, pH 7.4, and disrupted at 40C. The cell homogenates were centrifuged (1000 x g, 10 min), and the supernatant was subjected to ultracentrifugation (20,000 x g, 1 h). The pellet was then resuspended in 2.3% SDS/62.5 mM Tris/10%6 glycerol/5% 2-mercaptoethanol, pH 6.8. One-dimensional gel electrophoresis and electrotransfers to nitrocellulose filters were performed as described by Laemmli (22) and Burnette (23). Two-dimensional SDS/PAGE was performed as described by O'Farrell (24). The filters were soaked in 0.02 M TBS/3% gelatin, washed in 0.05% Tween 20/0.02 M TBS, and then incubated with the test sera or ascitic fluid diluted 1:50 in 1% gelatin/0.05% Tween 20/0.02 M TBS. After washing, they were incubated with biotinylated sheep antiAbbreviations: NOD, nonobese diabetic; TBS, Tris-buffered saline; PBS, phosphate-buffered saline; NCS, newborn calf serum; MHC, major histocompatibility complex. tTo whom reprint requests should be addressed. 172The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Prevention of diabetes in nonobese diabetic mice by anti-I-A monoclonal antibodies: transfer of protection by splenic T cells.

Cited by 111 publications

References 43 publications

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1.

Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products.

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