Researchers at the Johns Hopkins Bloomberg School of Public Health have determined that neurons in the central nervous system react differently to the body's immune defenses to rid themselves of viruses that cause encephalitis, such as West Nile and Eastern Equine Encephalitis viruses. Encephalitis is an inflammation of the brain and can cause neurological problems including, seizures, coma, and death.
In a study published in the July 13, 2001 issue of Science, researchers discovered that T-cells produce a protein, interferon-g, which can clear the virus in neurons located in the spinal cord and brain stem, but not in neurons located in the cerebral cortex. Neurons are cells that conduct and generate electrical impulses to carry information throughout the central nervous system. The findings add to the understanding of lymphocytes in the immune system and interactions of the central nervous system and could lead to new approaches to the treatment of viral encephalitis.
"Our previous research indicated that antibodies successfully clear infection from the central nervous system. With this study, we wanted to see if lymphocytes could also clear viral infections from the neurons," says Diane Griffin, MD, PhD, professor and chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. "Normally, T-cells control virus infections by destroying infected cells, but that would be counterproductive for neurons, because the body does not make new neurons," explains Dr. Griffin.
For the study, the researchers observed mice that did not have the ability to produce antibodies and compared them to normal mice. The mice were infected with Sindbis virus, a mosquito-borne virus related to other causes of encephalitis transmitted by mosquitoes, such as West Nile and Eastern Equine encephalitis viruses.
During the experiments, Gwendolyn Binder, a graduate student in the laboratory of Dr. Griffin, observed that CD4 and CD8 T-cells both successfully cleared the virus from the neurons from the spinal cord and brain stem using interferon-g. However, the neurons in the brain cortex did not react to the interferon-g in the same manner. This indicated a site-specific response to this clearance mechanism among the neurons. In addition, the researchers observed that another protein, TNF-a, produced by the T-cells was unable to clear the virus from the central nervous system.
"This research shows that virus-infected neurons do not all respond to the lymphocyte immune system in the same way to clear infection. Therefore, different combinations of antibody and T-cell immunity may be needed for control of infection and recovery from encephalitis depending on the parts of the brain or spinal cord that are infected," adds Dr. Griffin.
B. Schofield assisted with imaging and photography for the study. Support was provided by grants from the Markey Foundation (G.K.B.) and from the National Institute of Neurological Diseases and Stroke (D.E.G.).