Suppression of Overt Diabetes in NOD Mice by Anti-thymocyte Serum or Anti-Thy 1, 2 Antibody

Harada, Minoru; Makino, Susumu

doi:10.1538/expanim1978.35.4_501

Cited by 59 publications

(21 citation statements)

References 3 publications

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“…As in human diabetes, the NOD mouse exhibits a T cell-mediated destruction of the islet ␤ cells of the pancreas (3)(4)(5)(6)(7)(8)(9)(10)(11). To understand the role of T cells in diabetes in the NOD mouse, isletspecific T cell clones have been produced by several groups (1,(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Induction Of Diabetes In Nonobese Diabetic Mice By Th2 T Celmentioning

confidence: 99%

Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse

Poulin

Haskins

2000

The Journal of Immunology

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We have produced a panel of cloned T cell lines from the BDC-2.5 TCR transgenic (Tg) mouse that exhibit a Th2 cytokine phenotype in vitro but are highly diabetogenic in vivo. Unlike an earlier report in which T cells obtained from the Tg mouse were cultured for 1 wk under Th2-promoting conditions and were found to induce disease only in NOD.scid recipients, we found that long-term T cell clones with a fixed Th2 cytokine profile can transfer disease only to young nonobese diabetic (NOD) mice and never to NOD.scid recipients. Furthermore, the mechanism by which diabetes is transferred by a Tg Th2 T cell clone differs from that of the original CD4+ Th1 BDC-2.5 T cell clone made in this laboratory. Whereas the BDC-2.5 clone rapidly causes disease in NOD.scid recipients less than 2 wk old, the Tg Th2 T cell clones can do so only when cotransferred with other diabetogenic T cells, suggesting that the Th2 T cell requires the presence of host T cells for initiation of disease.

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Section: Induction Of Diabetes In Nonobese Diabetic Mice By Th2 T Celmentioning

confidence: 99%

Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse

Poulin

Haskins

2000

The Journal of Immunology

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“…NOD mice develop the infiltration of mononuclear cells around and within pancreatic islets (insulitis) by 5-6 wk of age that may later progress to the destruction of fi-cells and overt diabetes (2). Although the important role of T-lymphocyte-dependent autoimmunity in the development of insulitis and overt diabetes has been demonstrated in this animal model (3)(4)(5), neither the triggering events nor the pathway of p-cell destruction, including direct effector cells, have been fully elucidated. The likely candidates directly responsible for p-cell destruction are macrophages, natural killer (NK) cells, and cytotoxic T lymphocytes (CTLs) (6)(7)(8).…”

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confidence: 90%

Prevention of Cyclophosphamide-Induced and Spontaneous Diabetes in NOD/Shi/Kbe Mice by Anti-MHC Class I Kd Monoclonal Antibody

et al. 1991

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The immune mechanisms directly responsible for beta-cell destruction in insulin-dependent diabetes are undefined. We studied the role of MHC class I-restricted T lymphocytes in the development of diabetes in cyclophosphamide (CY)-treated male and untreated female NOD mice (H-2Kd,Db). After administration of CY to 10-wk-old male NOD/Shi/Kbe mice, 37 of 64 (58%) phosphate-buffered saline-injected control mice and 13 of 22 (59%) anti-Kb and 12 of 27 (44%) anti-Db monoclonal antibody (MoAb)-injected mice became diabetic by 14 wk of age, whereas only 3 of 38 (8%) anti-Kd and 2 of 13 (15%) anti-Lyt-2 MoAb-injected mice did. In untreated female NOD/Shi/Kbe mice, 30 of 46 (65%) mice developed spontaneous diabetes by 30 wk of age, whereas none of 9 anti-Kd MoAb-injected mice became diabetic. Immunohistochemical studies showed that islet-infiltrating cells in CY-treated control mice were composed mainly of both L3T4+ and Lyt-2+ T lymphocytes, whereas many L3T4+ and very few Lyt-2+ lymphocytes infiltrated within the islets in anti-Kd MoAb-injected mice. Administration of anti-Lyt-2 MoAb induced the absence of Lyt-2+ T lymphocytes in the islet and spleen. However, anti-Kd MoAb did not change the number of spleen cells or the T-lymphocyte subset and response to concanavalin A. These results suggest that MHC class I Kd-restricted Lyt-2+ T lymphocytes play an important role as direct effector cells in destruction of beta-cells in NOD/Shi/Kbe mice.

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“…In these mice, a pancreatic inflammation consisting of mononudear leukocytes first surrounds and then infiltrates the islets and destroys the insulin-producing 13 cells (2). T cells play a pivotal role in the development of this disease, as demonstrated by antibody treatment (3)(4)(5)(6) and splenocyte transfer experiments (7,8).…”

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confidence: 99%

Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice.

Mueller

Krahl

Sarvetnick

1996

The Journal of Experimental Medicine

291

143

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SummaryDiabetes in nonobese diabetic (NOD) mice is a T cell-dependent autoimmune disease. The destructive activities of autoreactive T cells have been shown to be tightly regulated by effector molecules. In particular, T helper (Th) 1 cytokines have been linked to diabetes pathogenesis, whereas Th2 cytokines and the cells that release them have been postulated to be protective from disease. To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic [3 cells under the control of the human insulin promoter. We found that transgenic NOD-IL-4 mice, both females and males, were completely protected from insulitis and diabetes. Induction of functional tolerance to islet antigens in these mice was indicated by their inability to reject syngeneic pancreatic islets and the failure of diabetogenic spleen cells to induce diabetes in transgenic NOD-IL-4 recipients. Interestingly, however, islet expression of IL-4 was incapable of preventing islet rejection in overfly diabetic NOD recipient mice. These results demonstrate that the Th2 cytokine IL-4 can prevent the development of autoimmunity and destructive autoreactivity in the NOD mouse. Its ability to regulate the disease process in the periphery also indicates that autoimmune diabetes in NOD mice is not a systemic disease, and it can be modulated from the islet compartment.

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Suppression of Overt Diabetes in NOD Mice by Anti-thymocyte Serum or Anti-Thy 1, 2 Antibody

Cited by 59 publications

References 3 publications

Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse

Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse

Prevention of Cyclophosphamide-Induced and Spontaneous Diabetes in NOD/Shi/Kbe Mice by Anti-MHC Class I Kd Monoclonal Antibody

Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice.

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