Summary: Some of the T cell epitopes targeting myelin in monkeys were the same as those found in humans with multiple sclerosis. Researchers say linking these specific cells opens the doors to developing antiviral therapies that could be useful to treat newly diagnosed cases of MS in humans.
Source: Oregon Health and Science University
Scientists have uncovered new clues implicating a type of herpes virus as the cause of a central nervous system disease in monkeys that’s similar to multiple sclerosis in people.
The findings, published in the Annals of Clinical and Translational Neurology, expand on previous work to understand the cause of the disease and potentially develop antiviral therapies. The work was led by scientists at Oregon Health & Science University.
“This gives us a better understanding of the model,” said Scott Wong, Ph.D., senior author of the study and a scientist at the OHSU Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center. “It draws more parallels to MS in people.”
The new study reveals the presence of two kinds of T cells, a type of white blood cell that’s a critical part of the body’s immune system. In this case, scientists determined the T cells were associated with an immune response involving the loss of myelin, the protective sheath that covers nerve fibers.
Myelin and nerve fibers become damaged in multiple sclerosis, which slows or blocks electrical signals required for us to see, move our muscles, feel sensations and think.
“We found that some of the T cell epitopes targeting myelin in these animals are identical to those found in humans with MS,” Wong said.
By linking these specific T cells to the loss of myelin, scientists say the new study opens the possibility of developing an antiviral therapy that could be especially useful for newly diagnosed cases of multiple sclerosis.
“If we found a unique virus that we believed was causing MS, then you could in theory come up with a vaccine against that virus,” said co-author Dennis Bourdette, M.D., professor emeritus and former chair of neurology in the OHSU School of Medicine.
The work builds on a chance discovery in the colony of Japanese macaques at the primate center.
In 2011, scientists at OHSU published research identifying a group of monkeys at the primate center with a naturally occurring disease known as Japanese macaque encephalomyelitis. Since then, scientists have been working to understand the cause and progression of the disease in the macaques with an eye toward applying possible therapies in people.
The latest study points toward developing strategies to combat the disease leveraging the body’s immune response.
“If we can understand how it’s doing it, we may be able to test vaccine strategies,” Wong said. “I’m not sure we can prevent virus infection, but we may be able to prevent virus-associated disease.”
Funding: This research was supported by the U.S. Department of Defense award numbers W81XWH-09-1-0276 and W81XWH-17-1-0101; the National Institutes of Health, award numbers P51OD011092 and R24-NS104161; the Laura Fund for Multiple Sclerosis Research; and the Race to Erase MS.
Myelin‐specific T cells in animals with Japanese macaque encephalomyelitis
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.
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.
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.
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.