Prevention of diabetes in NOD mice treated with antibody to murine IFNγ

Debray-Sachs, M; Carnaud, Claude; Boîtard, Christian; Cohen, H.; Gresser, Ion; Bédossa, Pierre; Bach, Jean‐François

doi:10.1016/0896-8411(91)90021-4

Cited by 237 publications

(114 citation statements)

References 36 publications

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“…IFN-γ neutralization, however, marked by reduced CXCL9 and 10 ( Figure 5, B and C) and increased CXCL13 ( Figure 5D) was insufficient to reverse established insulitis ( Figure 5A). Anti-IFN-γ Ab has been reported to be similarly ineffective in NOD mice once islet T cell residency is established (51). Lack of an effect on insulitis by anti-IFN-γ Ab is likely due to a compensatory increase in the expression of T H 1 chemokines not directly regulated by IFN-γ, such as CCL2, 3, 4, and 5 ( Figure 5, H-K).…”

Section: Discussionmentioning

confidence: 99%

Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

et al. 2016

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“…Indeed, TH2 cells have been reported to transfer diabetes into NOD mice, but only if these animals are immunocompromised (5). The bulk of evidence implicates a TH1-driven type of immunopathology as the dominant force in the development of IDDM (14)(15)(16)(17)(18)(19)(20)(21)(22)(23), arguing that the lack of IL-4R␣ does not mediate its effect by diminishing TH2 effector functions.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, IFN-␥-producing TH1 clones derived from CD4 cells isolated from the pancreas of nonobese diabetic (NOD) mice transfer the disease to young NOD mice (11)(12)(13). In NOD mice, anti-IFN-␥ antibodies have been reported to block the onset of cyclophosphamideinduced diabetes (14) or of diabetes induced by splenocyte transfer (15). However, a targeted mutation in the IFN-␥ gene has been reported to delay but not prevent the onset of diabetes in NOD mice (16).…”

mentioning

confidence: 99%

A targeted mutation in the IL-4Rα gene protects mice against autoimmune diabetes

Radu

Noben-Trauth

Hu‐Li

et al. 2000

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

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Autoimmune insulin-dependent diabetes mellitus (IDDM) occurs spontaneously in mice-bearing transgenes encoding the influenza hemagglutinin under the control of the rat insulin promoter and a T cell receptor specific for an hemagglutinin peptide associated with I-E d . Such ''double transgenic'' mice expressing wild-type or targeted IL-4R␣ genes were examined for the onset of IDDM. Eight of 11 mice homozygous for wild-type IL-4R␣ were hyperglycemic by 8 weeks of age, whereas only 1 of 16 mice homozygous for the targeted allele were hyperglycemic at this time. Most 1L-4R␣؊͞؊ mice remained normoglycemic to 36 weeks of age. Although only 10% of double transgenic mice homozygous for the wild-type IL-4R␣ allele survived to 30 weeks, 80% of mice homozygous for the targeted allele did so. Heterozygous mice displayed an intermediate frequency of diabetes. Even as late as 270 days of age, mice homozygous for the targeted allele had no insulitis or only peri-insulitis. Thus, the inability to respond to IL-4 and͞or IL-13 protects mice against IDDM in this model of autoimmunity.

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“…Conversely, diabetes is delayed by systemic treatment with anti-IFN-+ mAb or IL-12 antagonists [12,13].…”

Section: Introductionmentioning

confidence: 99%

Exacerbated Th2‐mediated airway inflammation and hyperresponsiveness in autoimmune diabetes‐prone NOD mice: a critical role for CD1d‐dependent NKT cells

et al. 2004

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The NOD mouse has proved to be a relevant model of insulin-dependent diabetes mellitus, closely resembling the human disease. However, it is unknown whether this strain presents a general bias toward Th1-mediated autoimmunity or remains capable of mounting complete Th2-mediated responses. Here, we show that NOD mice have the capacity to develop a typical Th2-mediated disease, namely experimental allergic asthma. In contrast to what might have been expected, they even developed a stronger Th2-mediated pulmonary inflammatory response than BALB/c mice, a strain that shows a typical Th2 bias in this model. Thus, after allergen sensitization and intra-nasal challenge, the typical features of experimental asthma were exacerbated in NOD mice, including enhanced bronchopulmonary responsiveness, mucus production and eosinophilic inflammation in the lungs as well as specific IgE titers in serum. These hallmarks of allergic asthma were associated with increased IL-4, IL-5, IL-13 and eotaxin production in the lungs, as compared with BALB/c mice. Notwithstanding their quantitative and functional defect in NOD mice, CD1d-dependent NKT cells contribute to aggravate the disease, since in OVA-immunized CD1d -/-NOD mice, which are deficient in this particular T cell subset, airway eosinophilia was clearly diminished relative to NOD littermates. This is the first evidence that autoimmune diabetesprone NOD mice can also give rise to enhanced Th2-mediated responses and might thus provide a useful model for the study of common genetic and cellular components, including NKT cells that contribute to both asthma and type 1 diabetes.

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Prevention of diabetes in NOD mice treated with antibody to murine IFNγ

Cited by 237 publications

References 36 publications

Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

A targeted mutation in the IL-4Rα gene protects mice against autoimmune diabetes

Exacerbated Th2‐mediated airway inflammation and hyperresponsiveness in autoimmune diabetes‐prone NOD mice: a critical role for CD1d‐dependent NKT cells

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