Regulation of autoimmune diabetes: Characteristics of non‐islet‐antigen specific therapies

Gazda, Lawrence S.; Baxter, Alan G.; Lafferty, Kevin J.

doi:10.1038/icb.1996.69

Cited by 13 publications

(6 citation statements)

References 33 publications

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“…The repeated epicutanous application of the contact allergens gave a local harmless subclinical dermatitis. The application involved only the outside of the ears, which is in contrast to the systemic and immunological unspecific treatments with anti-CD3 [32] and complete Freund's adjuvant [33] or the systemic treatment with BCG vaccination [34].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

et al. 2010

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BackgroundType 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutanous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases.MethodNOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation.ResultsIt was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine.ConclusionThe study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site.The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutanous procedure may lead to new strategies in prevention of type 1 diabetes in humans.

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Section: Discussionmentioning

confidence: 99%

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

et al. 2010

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“…Evidence indicates that Th1-mediated autoimmunity can be downregulated by infectious pathogens such as mycobacteria (13,16,22,34,38). Several regulatory pathways have been suggested to mediate this downregulation.…”

Section: Discussionmentioning

confidence: 99%

“…Also, both CFA and Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine were shown to block diabetes in nonobese diabetic (NOD) mice (16,29,37). BCG vaccine given to newly diagnosed human diabetics led to clinical remissions of various lengths in 11 of 17 cases (29).…”

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confidence: 99%

Infection withMycobacterium bovisBCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis

Sewell

Reinke

et al. 2003

Clin Vaccine Immunol

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Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection with Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG 35-55 ) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4 ؉ T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG 35-55 -specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG 35-55 ) CD4؉ T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated CNS antigen-specific CD4 ؉ T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.

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“…21 the apparent ineffectiveness of BCG for the prevention of t1Dm in humans might be explained by its much weaker immunostimulatory effect than FCa. 22 infection with a live, attenuated strain of Salmonella typhimurium was shown to prevent autoimmune diabetes in the noD mouse. 23 the protective mechanism was suggested to involve altered chemokine expression and priming and trafficking of t cells in the infected mice, leading to downregulation of auto reactive t cells.…”

Section: Methods Of Vaccination Against T1dmmentioning

confidence: 99%

Immunomodulation with microbial vaccines to prevent type 1 diabetes mellitus

Petrovsky

2010

Nat Rev Endocrinol

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Selected bacteria, viruses, parasites and nonliving, immunologically active microbial substances prevent autoimmune diabetes in animal models. Such agents might also have a protective effect in humans by providing immune stimuli critical during childhood development. The 'hygiene hypothesis' proposes that reduced exposure to environmental stimuli, including microbes, underlies the rising incidence of childhood autoimmune diseases, including type 1 diabetes mellitus (T1DM). This hypothesis is supported by data that highlight the importance of infant exposure to environmental microbes for appropriate development of the immune system, which might explain the observation that administration of microbes or their components inhibits autoimmune disease in animals. This finding raises the possibility of using live, nonpathogenic microbes (for example, probiotics) or microbial components to modulate or 're-educate' the immune system and thereby vaccinate against T1DM. Progress has been assisted by the identification of receptors and pathways through which gut microbes influence development of the immune system. Such mechanistic data have moved a field that was once regarded as being on the scientific fringe to the mainstream, and support increased funding to advance this promising area of research in the hope that it might deliver the long awaited answer of how to safely prevent T1DM.

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Regulation of autoimmune diabetes: Characteristics of non‐islet‐antigen specific therapies

Cited by 13 publications

References 33 publications

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

Infection withMycobacterium bovisBCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis

Immunomodulation with microbial vaccines to prevent type 1 diabetes mellitus

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