T Cell-Dependent Class II Major Histocompatibility Complex Antigen Expression in vivo Induced by the Diabotegen Streptozotocin

Klinkhammer, Christiane; Dohle, Claudia; Gleichmann, Helga

doi:10.1016/s0171-2985(89)80025-7

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…The observed increase of IFN-+ -producing cells may explain why STZ increases expression of MHC class I and II molecules [7,30] and agrees with data indicating selective expression of IFN-+ mRNA in monocytes isolated from inflamed islets of mice receiving multiple injections of STZ [31]. However, actual production of IFN-+ was not measured in these studies and the producing cells could not be characterized.…”

Section: Discussionsupporting

confidence: 72%

Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2

et al. 1998

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Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (self) epitopes for which tolerance has not been established, while simultaneously providing the necessary adjuvant activity. The resulting response type is influenced by the genotype of exposed individuals and relates to susceptibility to the adverse immune effects of the chemicals. Here, we assessed the modulatory role of the chemical compounds themselves. A single injection of streptozotocin (STZ) increased the number of CD8+ cells, macrophages, apoptotic cells, and IFN-gamma-producing T helper and T cytotoxic cells, whereas the number of CD4+ cells and B cells was reduced in the draining lymph node. Coinjection with the reporter antigen TNP-OVA resulted in primary and secondary production of TNP-specific antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA. Injection of HgCl2 on the other hand, reduced the number of IFN-gamma-producing cells, induced accumulation of B cells and CD4+ and CD8+ T cells, enhanced IgG1 and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production as well as for DTH reactions. Together these results indicate that a single injection of STZ stimulates type-1 responses, whereas HgCl2 enhanced mixed type-1 and -2 responses in BALB/c mice. These response types match the (auto)immune effects elicited to unknown (auto)antigens following multiple injections of these chemicals.

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Section: Discussionsupporting

confidence: 72%

Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2

et al. 1998

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“…In the LD-STZ mouse model of experimental hyperglycemia developed by Like and Rossini (10), STZ exerts two different effects, namely direct (3-cell toxicity (9)(10)(11)(12)(13)(14)(15)(16) and, in susceptible strains T-cell-dependent immune reactions (17)(18)(19)(20)(21)(22)(23). When toxic and immunological effects act in concert, hyperglycemia is preceded by insulitis (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: -T-g Was Documented By Assaying For Basal and Glucose-stimumentioning

confidence: 99%

“…When toxic and immunological effects act in concert, hyperglycemia is preceded by insulitis (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). With regard to the immunological effects of STZ, it has been demonstrated previously that STZ induces specific immune reactions by T-cells (21).…”

Section: -T-g Was Documented By Assaying For Basal and Glucose-stimumentioning

confidence: 99%

Prevention of High- and Low-Dose STZ-Induced Diabetes With D-Glucose and 5-Thio-D-Glucose

Wang

Dohle²,

Friemann³

et al. 1993

Diabetes

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To induce hyperglycemia in mice by administration of STZ, two experimental protocols that involve different pathogenic pathways are being used. First, the intraperitoneal injection of a single high dose (HD-STZ) exerts direct toxicity on beta-cells, which results in necrosis within 48-72 h and overt permanent hyperglycemia. Second, injections of multiple low doses of STZ (LD-STZ), administered intraperitoneally on 5 consecutive days, induce both beta-cytotoxic effects and STZ-specific T-cell-dependent immune reactions. In LD-STZ models, only a combination of toxic and immunological effects result in gradually increasing hyperglycemia, provided male mice of susceptible strains are being used. In this study, we found that 5-T-G, a glucose analogue that has sulfur for oxygen in the pyranose ring, prevented, in a dose-dependent way, both HD-STZ- and LD-STZ-induced hyperglycemia and that D-G, which was only tested in the LD-STZ system, was also protective, albeit somewhat less so than 5-T-G. This protective effect was achieved by intraperitoneally injecting 5-T-G and D-G, respectively, right before each STZ injection. Protection against hyperglycemia was already achieved with a total of 3 injections of 5-T-G, 1 injection each given before the first 3 of 5 LD-STZ injections. By means of OGTT, it was determined that pretreatment with 5-T-G afforded protection from substantial beta-cell damage in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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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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T Cell-Dependent Class II Major Histocompatibility Complex Antigen Expression in vivo Induced by the Diabotegen Streptozotocin

Cited by 9 publications

References 27 publications

Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2

Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2

Prevention of High- and Low-Dose STZ-Induced Diabetes With D-Glucose and 5-Thio-D-Glucose

Streptozotocin-induced diabetes in mice lacking αβ T cells

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