Interferon-Gamma's Link to MS Is Determined by Location

A recent publication described the creation of a line of genetically engineered mice lacking receptors for interferon-gamma that was utilized to study the role of this cytokine in the development of multiple sclerosis (MS).

MS is an autoimmune disease that is perceived when the nervous system has been sufficiently injured by the body's own immune cells. While the spinal cord is one potential site of autoimmune damage, the most serious cases of MS occur when the immune system specifically targets the cerebellum, the part of the brain responsible for sensory perception, coordination, and movement control.

In the current study, investigators at the Washington University School of Medicine (St. Louis, MO, USA) studied the involvement of T-cell produced interferon-gamma in the development of MS. For this purpose, they created a line of mice that lacked interferon-gamma receptors and could not respond to interferon-gamma in any fashion.

Immune cells taken from unmodified mice with an MS-like disease were injected into the genetically engineered animals. Results published in the October 2008 issue of the Journal of Experimental Medicine (JEM) revealed that the injected T-cells were transported into the cerebellum and brain stem where they initiated nerve cell damage leading to an MS-like disease. In contrast, similar immune cells were prevented from entering the brains of mice with normal interferon-gamma recognition. Therefore, interferon-gamma was required to prevent the development of MS in the brain.

Results from the spinal cord were quite different. In the genetically engineered mice without interferon recognition, the immune cells were unable to initiate spinal cord inflammation, and no damage occurred. In normal mice with intact interferon-gamma recognition, activated and injected immune cells were able to enter the spinal cord and cause injury. Interferon-gamma failed to protect against autoimmune damage at this location.

"Our research shows that certain characteristics inherent in different regions of the brain and spinal cord can provoke immune attacks on nerve cells,” explained senior author Dr. John H. Russell, professor of developmental biology at the Washington University School of Medicine. "An understanding of the mechanisms involved in immune system invasion of the nervous system may allow development of better models for determining prognosis and treating many neurological diseases such as multiple sclerosis. Down the road, we would like to investigate whether we can prevent disease in the cerebellum in mice if we promote interferon production in that brain region. One way to do that would be to use gene therapy to insert a gene that would increase interferon in the mice's brains. Then we would test the mice to see if they gained protection against MS-like disease.”

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Washington University School of Medicine