Induction of experimental allergic encephalomyelitis in the NIH minipig
B A Singer1, N J Tresser, J A Frank
1Neuroimmunology Branch, National Institute of Neurological Disease and Stroke National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 5B16, Bethesda, MA 20892, USA. bnvsinger@earthlink.net
Abstract:
Experimental allergic encephalomyelitis (EAE) was induced in the NIH minipig to create a large animal model of multiple sclerosis with a well-characterized immune system. Sixteen NIH minipigs were inoculated with minipig spinal cord homogenate (SCH). The clinical course was primarily monophasic, but re-induction was possible. CNS and blood lymphocytes specifically proliferated to SCH. Flow cytometry of CNS-isolated cells and SCH-stimulated PBMC revealed a shift to CD4(+) CD8(+) cells. Pathology demonstrated demyelination in the CNS white matter with perivascular mononuclear cell infiltrates of CD3(+)CD4(+)CD45(+) lymphocytes with a subset CD8(+). Pathology and in vitro SCH responses implicate a central role of CD4(+) lymphocytes in swine EAE.
Insights
NIH minipigs developed experimental allergic encephalomyelitis (EAE), a large animal model for multiple sclerosis. This study highlights the role of CD4+ lymphocytes in the disease progression and immune response.
Area of Science:
- Neuroimmunology
- Veterinary Pathology
- Animal Models of Disease
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS).
- Developing suitable animal models is crucial for understanding MS pathogenesis and testing therapies.
- The NIH minipig offers a large animal model with a well-characterized immune system.
Purpose of the Study:
- To establish and characterize experimental allergic encephalomyelitis (EAE) in NIH minipigs as a large animal model for MS.
- To investigate the immune response and pathological features of EAE in this model.
Main Methods:
- Induction of EAE by inoculating NIH minipigs with minipig spinal cord homogenate (SCH).
- Monitoring clinical course and assessing disease re-inducibility.
- Analyzing CNS and blood lymphocyte proliferation in response to SCH.
- Utilizing flow cytometry to characterize immune cell populations (CD4+, CD8+, CD45+) in the CNS and peripheral blood.
- Histopathological examination of CNS tissue to identify demyelination and inflammatory infiltrates.
Main Results:
- EAE was successfully induced in NIH minipigs, primarily presenting a monophasic clinical course with potential for re-induction.
- Specific proliferation of CNS and blood lymphocytes to SCH was observed.
- Flow cytometry revealed a shift towards CD4+ CD8+ cells in CNS-isolated cells and SCH-stimulated peripheral blood mononuclear cells (PBMCs).
- Pathology confirmed demyelination in the CNS white matter with perivascular infiltrates of CD3+CD4+CD45+ lymphocytes, including a CD8+ subset.
Conclusions:
- The NIH minipig model of EAE successfully mimics key aspects of MS pathology.
- Both in vitro SCH responses and pathological findings implicate a central role for CD4+ lymphocytes in swine EAE.
- This model provides a valuable platform for future MS research.
