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Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis (EAE) Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge
Published on: April 9, 2012
Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity
J Goverman1, A Woods, L Larson
1Division of Biology, California Institute of Technology, Pasadena 91125.
Cell
|February 26, 1993
Summary
Researchers created a new mouse model for multiple sclerosis (MS) that spontaneously develops the disease. This model helps study genetic and environmental factors contributing to autoimmune conditions like MS.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Multiple sclerosis (MS) is a complex autoimmune disease affecting the central nervous system.
- Current animal models often require specific induction methods, limiting spontaneous disease study.
- Understanding genetic and environmental triggers is crucial for developing new MS therapies.
Purpose of the Study:
- To develop a novel transgenic mouse model that spontaneously develops autoimmune disease mimicking human multiple sclerosis.
- To investigate the role of autoreactive T cells specific for myelin basic protein (MBP) in disease development.
- To explore the interplay between genetic predisposition and environmental factors in spontaneous autoimmune pathogenesis.
Main Methods:
- Construction of transgenic mice expressing a rearranged T cell receptor specific for myelin basic protein (MBP).
- Assessment of T cell tolerance induction and presence of autoreactive T cells in lymphoid organs.
- Induction of experimental allergic encephalomyelitis (EAE) using MBP, adjuvant, and pertussis toxin.
- Comparison of spontaneous EAE development in mice housed in conventional versus specific pathogen-free (SPF) environments.
Main Results:
- Transgenic mice exhibited a lack of peripheral T cell tolerance and possessed functional, autoreactive T cells.
- Mice developed EAE upon immunization with MBP and adjuvant/pertussis toxin, or with pertussis toxin alone.
- Spontaneous EAE occurred in mice in non-sterile conditions but was prevented in a sterile, SPF environment.
- This indicates that environmental factors are critical for the spontaneous onset of autoimmune disease in this model.
Conclusions:
- The developed transgenic mouse model effectively recapitulates spontaneous autoimmune disease akin to human multiple sclerosis.
- Environmental factors, such as microbial exposure, play a significant role in triggering autoimmune disease in genetically susceptible individuals.
- This model provides a valuable platform for dissecting the complex genetic and environmental interactions underlying spontaneous autoimmune diseases.
