Myelin-specific T cells in animals with Japanese macaque encephalomyelitis
Aparna N Govindan1, Kristin S Fitzpatrick1, Minsha Manoharan1
1Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
Objective:
To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery.
Methods:
Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression.
Results:
Demyelinating JME lesions contained CD4+ T cells and CD8+ T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8+ T-cell responses were absent in JME peripheral blood, and in age- and sex-matched controls. However, CD4+ Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3+ T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFNγ responses.
Interpretations:
JME possesses an immune-mediated component that involves both CD4+ and CD8+ T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma-herpesvirus infection.
Insights
Japanese macaque encephalomyelitis (JME) involves myelin-specific T cells in the central nervous system and periphery. These findings offer insights into inflammatory demyelinating disease pathogenesis potentially linked to gamma-herpesvirus infection.
Area of Science:
- Neuroimmunology
- Veterinary Neurology
- Demyelinating Diseases
Background:
- Japanese macaque encephalomyelitis (JME) is a spontaneous demyelinating disease in macaques, serving as a model for multiple sclerosis (MS).
- Understanding the immunological underpinnings of JME is crucial for elucidating inflammatory demyelinating disease pathogenesis.
Purpose of the Study:
- To investigate the presence and characteristics of myelin-specific T cells in the central nervous system (CNS) and periphery of Japanese macaques with JME.
- To explore the role of T-cell responses, including CD4+ and CD8+ T cells, and cytokine expression (IL-17, IFNγ) in JME pathogenesis.
Main Methods:
- Analysis of mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs), and peripheral blood of JME-affected and control macaques.
- Detection of myelin-specific T cells targeting myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and proteolipid protein (PLP).
- Assessment of T-cell responses (CD4+, CD8+, Th1, Th17) and cytokine expression (IL-17, IFNγ).
Main Results:
- Demyelinating JME lesions contained CD4+ and CD8+ T cells specific for MOG, MBP, and PLP.
- CD8+ T-cell responses were absent in JME peripheral blood, but CD4+ Th1 and Th17 responses were detected.
- Cervical LN MNCs from most JME animals showed myelin-specific T cells not found in controls.
- Sequence analysis revealed similarities between myelin antigens and JM rhadinovirus (JMRV) open reading frames.
Conclusions:
- JME exhibits an immune-mediated component involving myelin-specific CD4+ and CD8+ T cells.
- JME pathogenesis may be linked to gamma-herpesvirus infection, offering insights into inflammatory demyelinating diseases.
More Related Videos
08:03Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
09:01Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis
Published on: November 17, 2020
