Administration of silica or monoclonal antibody to Thy-1 prevents low-dose streptozotocin-induced diabetes in mice

Oschilewski, M; E, Schwab; Kiesel, U; Opitz, Uta; Stünkel, K; Kolb-Bachofen, Victoria; Kolb, Hubert

doi:10.1016/0165-2478(86)90032-5

Cited by 49 publications

(27 citation statements)

References 14 publications

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“…Later, Kolb-Bachofen et al [18] demonstrated that, prior to onset of insulitis and diabetes, macrophages infiltrated the islets and they termed this "single cell insulitis". The same group also demonstrated that single cell insulitis played an important role in the onset of LDS diabetes by demonstrating that treatment with silica, a macrophage toxin, was more protective than T-cell depletion [19]. These findings, along with Leiter's [20] observations on LDS-treated SCID mice, implicated the macrophage in the early onset of LDS diabetes in mice.…”

Section: Discussionsupporting

confidence: 51%

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin

et al. 1997

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Section: Discussionsupporting

confidence: 51%

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin

et al. 1997

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“…Several lines of evidence suggest that the disease is T celldependent: (i) many antibodies reactive with lymphocytes, MHC or adhesion molecules have been found to inhibit STZ-induced insulitis and diabetes: anti-CD3 [1,2], -CD4, -CD8, Thy-1 [3][4][5], -Vb8 [6], -IL-2 receptor [7], -H-2A, H-2E [8][9][10] -LFA-1 [11]; (ii) cytokines are detectable in the pancreas before the onset of overt diabetes [12,13], and disease is inhibitable by treatment with an anti-interferon-gamma (IFN-g) antibody [13]; (iii) STZ has been found to induce the widespread expression of MHC class II [14][15][16][17]; (iv) in some [18], but not all [19], studies MHC congenic mice differ in their susceptibility to STZ-induced IDDM; (v) STZ injection has been reported to induce rat insulinoma cell linespecific cytotoxic T lymphocytes (CTL) [20]; (vi) a variety of immunosuppressant drugs have been found to inhibit disease [21]; (vii) B7.1 transgenic mice have an enhanced susceptibility to disease [22]; (viii) some stocks of athymic (nude) mice have proved relatively resistant to disease induction [23,24]; (ix) resistance to disease can be induced through the intrathymic transplantation of STZ-treated islet cells [25].…”

Section: Introductionmentioning

confidence: 99%

Streptozotocin-induced diabetes in mice lacking αβ T cells

Elliott

Dewchand

Altmann

1997

Clinical and Experimental Immunology

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SUMMARYMultiple low-dose streptozotocin (MD-STZ) is widely used for the experimental induction of diabetes, but, as non-obese diabetic (NOD)-scid/scid mice have been found to display enhanced susceptibility to MD-STZ, whether or not the model is genuinely autoimmune and T cell-mediated has been unclear. Mice bearing a targeted mutation of the T cell receptor (TCR) a-chain were therefore used to assess whether TCR ab + cells are involved in the diabetogenic effects of MD-STZ injections. Young NOD mice lacking TCR ab cells, when given five daily injections of 40 mg/kg STZ, developed diabetes at low frequency (2/12), despite the widespread destruction of pancreatic islet cells. By comparison, most normal control mice became hyperglycaemic (12/23). We conclude that whilst much of the tissue destruction observed in this model is due to the direct toxic effect of STZ, a significant amount is also due to the action of TCR ab cells tipping the balance between tolerable and clinically damaging action on islet cells.

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“…APCs play a critical role in type 1 diabetes by secreting beta cell cytotoxic cytokines and by presenting beta cell antigens to the immune system. The essential role of APCs has been demonstrated in studies on spontaneous (BioBreeding [BB] rats and NOD mice) and induced (multiple low dose streptozotocin [MLD-STZ]) animal models of type 1 diabetes [30][31][32]. Activation of APCs leads to the production and release of cytokines and reactive oxygen species (ROS), creating an inflammatory and oxidative milieu that may produce many changes in PTM.…”

Section: Introductionmentioning

confidence: 99%

Do post-translational beta cell protein modifications trigger type 1 diabetes?

et al. 2013

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Type 1 diabetes is considered an autoimmune disease characterised by specific T cell-mediated destruction of the insulin-producing beta cells. Yet, except for insulin, no beta cell-specific antigens have been discovered. This may imply that the autoantigens in type 1 diabetes exist in modified forms capable of specifically triggering beta cell destruction. In other immune-mediated diseases, autoantigens targeted by the immune system have undergone post-translational modification (PTM), thereby creating tissue-specific neo-epitopes. In a similar manner, PTM of beta cell proteins might create beta cell-specific neo-epitopes. We suggest that the current paradigm of type 1 diabetes as a classical autoimmune disease should be reconsidered since the immune response may not be directed against native beta cell proteins. A modified model for the pathogenetic events taking place in islets leading to the T cell attack against beta cells is presented. In this model, PTM plays a prominent role in triggering beta cell destruction. We discuss literature of relevance and perform genetic and human islet gene expression analyses. Both direct and circumstantial support for the involvement of PTM in type 1 diabetes exists in the published literature. Furthermore, we report that cytokines change the expression levels of several genes encoding proteins involved in PTM processes in human islets, and that there are type 1 diabetes-associated polymorphisms in a number of these. In conclusion, data from the literature and presented experimental data support the notion that PTM of beta cell proteins may be involved in triggering beta cell destruction in type 1 diabetes. If the beta cell antigens recognised by the immune system foremost come from modified proteins rather than native ones, the concept of type 1 diabetes as a classical autoimmune disease is open for debate.

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Administration of silica or monoclonal antibody to Thy-1 prevents low-dose streptozotocin-induced diabetes in mice

Cited by 49 publications

References 14 publications

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin

Streptozotocin-induced diabetes in mice lacking αβ T cells

Do post-translational beta cell protein modifications trigger type 1 diabetes?

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