A new study has said that in young adults afflicted with multiple sclerosis (MS), a virus infection can incite the body to attack its own nerve tissue by activating unusual, disease-fighting cells with receptors for both viral and nerve proteins.
The dual-receptor observation indicates how brain and spinal cord nerve damage could be triggered in susceptible young adults with MS.
University of Washington Department of Immunology scientists Qingyong "John" Ji, Antoine Perchellet, and Joan M. Goverman conducted the study,
This is thought to be the first study to reveal a mechanism for autoimmune disease that depends on destroyer immune cells expressing dual receptors for a normal protein made by the body and a pathogen.
People with multiple sclerosis might lose their ability to see, walk, or use their arms, depending on which nerves are affected.
In healthy people, the immune system is kept in check to tolerate the usual proteins and cells in the body, much like an eager watch dog is put on a leash and trained to ignore friends and neighbours, yet still protect the family.
"Autoimmunity is believed to arise from an accidental breakdown in this tolerance of the body's own proteins. This breakdown is triggered by something in the environment, most likely a pathogen," Nature quoted Goverman as saying.
In the new study, the researchers genetically engineered mice that over-produce a certain type of white blood cell from a group known as killer T cells.
The specific killer T cells examined in this study were CD8+ T cells.
Researchers engineered mice to over-produce CD8+cells that recognized myelin basic protein, a predominant protein in the myelin sheath that covers nerves.
The major question investigated in the study was whether the genetically engineered mice would exhibit a disease that resembled multiple sclerosis.
The researchers infected the mice with a virus that has itself been engineered to produce myelin basic protein.
This infection should activate the CD8+T cells to first attack the virally infected cells making myelin basic protein to eliminate the virus, then kill other cells that make myelin basic protein to wrap around nerves.
Killing those cells would destroy the myelin sheath.
As expected, the mice developed a multiple sclerosis-like disease.
But the researchers were surprised when viruses lacking the myelin basic protein also triggered the disease.
Additional cross-breeding experiments revealed the existence of two receptors on a few of the CD8+T cells.
These cells, engineered specifically to bind to myelin basic protein, also built their own receptors for viruses, and could recognize both.
When exposed to cells infected with viruses, they would bind to and destroy them using one receptor.
In fact, some of these double-agent cells then would head elsewhere to bind their other receptor to cells producing myelin basic protein and ruin the coats on nerve cells.
"These results demonstrate a role for dual-receptor cells in autoimmunity," noted the authors.
The study also points to why a ubiquitous viral infection could leave most people without any lasting effects, but trigger autoimmunity in genetically predisposed individuals.
The findings open a new perspective on the proposal that multiple sclerosis is virally induced, despite the inability to detect infectious virus in the central nervous system of multiple sclerosis patients.
The study was published in Nature Immunology.