Animal models of autoimmunity

Howell, Charles D.

doi:10.1016/s1089-3261(02)00026-0

Cited by 12 publications

(3 citation statements)

References 34 publications

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“…Progress in developing new treatments for autoimmune hepatitis has been hindered by the lack of a credible animal model of the human disease [70,71]. Studies in various mouse models established the importance of T lymphocytes in causing liver injury, revealed mechanisms of antigen presentation, catalogued the identity of putative autoantigens, and described cytokine pathways and other counter-regulatory mechanisms affecting lymphocyte differentiation and proliferation [72].…”

Section: Progress Toward An Animal Modelmentioning

confidence: 99%

“…These murine models of liver inflammation and immune reactivity were invaluable in describing the pathogenic mechanisms of autoimmune hepatitis, but they were inadequate for evaluating new therapies. Immunizations using crude adjuvants provoked high frequencies of liver injury in control animals [70]; highly perturbed and inbred animals had short life-spans [70]; chronic inflammation and progression to cirrhosis could not be established [71,73]; triggering antigens were of uncertain relevance to the human disease [73]; and conclusions were often model-and antigen-dependent [73]. The limitations of these earlier models have been largely resolved, and there has been progress toward a durable animal model of the human disease.…”

Section: Progress Toward An Animal Modelmentioning

confidence: 99%

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Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis

Czaja

2010

Dig Dis Sci

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Current corticosteroid-based treatments of autoimmune hepatitis frequently have incomplete or unsatisfactory outcomes, side effects, and excessive immune suppression. The goal of this review is to describe the advances in developing animal models of autoimmune hepatitis and in treating diverse immune-mediated diseases that make pursuit of site-specific molecular and cellular inventions in autoimmune hepatitis feasible. Prime source and review articles in English were selected by a Medline search through October 2009. A murine model infected with an adenovirus expressing human CYP2D6 is a resource for evaluating new therapies because of its histological and serological features, persistence, and progressive hepatic fibrosis. Synthetic analog peptides that block autoantigen expression, a dimeric recombinant human fusion protein of cytotoxic T lymphocyte antigen-4, monoclonal antibodies against tumor necrosis factor-alpha, recombinant interleukin 10, tolerization techniques for disease-triggering autoantigens, T regulatory cell transfer, vaccination against antigen-specific cytotoxic CD8+ T cells, and gene silencing methods using small inhibitory RNAs are feasible interventions to explore. Treatments directed at dampening immunocyte activation with soluble cytotoxic T lymphocyte antigen-4, inhibiting immunocyte differentiation with recombinant interleukin 10, and improving immunosuppressive activity with regulatory T cell modulation have the most immediate promise. Progress in the development of an animal model of autoimmune hepatitis and experiences in other immune-mediated diseases justify the evaluation of site-specific molecular and cellular interventions in this disease.

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Section: Progress Toward An Animal Modelmentioning

confidence: 99%

Section: Progress Toward An Animal Modelmentioning

confidence: 99%

Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis

Czaja

2010

Dig Dis Sci

View full text Add to dashboard Cite

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“…Of course, to get an insight into the human conditions we are more interested in pathologies that occur spontaneously, in absence of adjuvants that inevitably interfere with the progression of the resulting disease [2]. Furthermore, the autoimmune diseases occurring upon immunization have a kinetic that is very different from the spontaneous disease, being more severe at start and often self-resolving after a few weeks [3]. The use of adjuvant is however often employed because autoantigen-specific TCR transgenic mice frequently fail to develop disease spontaneously, but only following specific immunization with antigen and adjuvant [4e6].…”

Section: Introductionmentioning

confidence: 99%