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Updated: Jul 5, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Oligodendrocyte-specific protein is encephalitogenic in rhesus macaques and induces specific demyelination of the
Jeffrey J Bajramovic1, Herbert P M Brok, Boudewijn Ouwerling
1Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. bajramovic@bprc.nl
Abstract:
Oligodendrocyte-specific protein (OSP) is a candidate autoantigen in the development of multiple sclerosis (MS). We evaluated the potential of OSP to induce EAE in rhesus monkeys, an out bred animal model for MS that is immunologically close to humans. Since OSP is a four-membrane spanning protein with highly hydrophobic regions, we synthesized recombinant proteins encompassing only the hydrophilic regions of human OSP (soluble (s)hOSP). Immunization with shOSP proteins induced clinical signs and histological features of optic neuritis in four out of ten rhesus monkeys. The development of clinical disease was associated with the presence of a strong cellular proliferative response to the immunizing shOSP protein. Analysis of the cellular responses in combination with neuropathological observations also indicates an important role for neutrophils in the disease process. Interestingly, all immunized monkeys developed antibody responses to OSP peptide 103-123, a B cell epitope previously identified in MS patients. These responses did not correlate with the development of clinical disease, but may have relevance as a biomarker for immunoreactivity towards OSP in myelin disorders. Our data demonstrate that in rhesus monkeys immune responses directed at OSP are encephalitogenic, leading to inflammatory responses throughout the central nervous system and to selective demyelination of the optic nerve.
Insights
Oligodendrocyte-specific protein (OSP) can trigger experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys, mimicking multiple sclerosis (MS) pathology. Immune responses to OSP cause central nervous system inflammation and optic nerve demyelination.
Area of Science:
- Neuroimmunology
- Autoimmunity
- Demyelinating diseases
Background:
- Oligodendrocyte-specific protein (OSP) is implicated as an autoantigen in multiple sclerosis (MS).
- Rhesus monkeys serve as a relevant outbred animal model for MS due to their immunological similarity to humans.
Purpose of the Study:
- To investigate the encephalitogenic potential of OSP in inducing experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys.
- To characterize the immune responses and neuropathological outcomes following OSP immunization.
Main Methods:
- Synthesis of soluble, hydrophilic regions of human OSP (shOSP) for immunization.
- Induction of EAE in rhesus monkeys via shOSP immunization.
- Assessment of clinical signs, cellular proliferative responses, antibody production, and neuropathology.
Main Results:
- Immunization with shOSP induced clinical signs and optic neuritis in 4/10 rhesus monkeys.
- Clinical disease correlated with strong cellular proliferative responses to shOSP.
- Neutrophils were identified as playing a significant role in the disease process.
- All monkeys developed antibodies to OSP peptide 103-123, a known B cell epitope in MS patients.
Conclusions:
- Immune responses targeting OSP are encephalitogenic in rhesus monkeys, causing CNS inflammation and optic nerve demyelination.
- OSP is a potential target autoantigen for MS.
- Antibody responses to OSP peptide 103-123 may serve as a biomarker for OSP immunoreactivity.
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