A cross-section of mouse dorsal root ganglia stained for memory CD4 T cells (green) and the vascular cell adhesion molecule, VCAM-1 (red) after six days of genital herpes challenge. Credit: Norifumi Iijima
Yale scientists have solved a puzzle of the immune system – how antibodies enter the nervous system to control viral infections. Their finding may have implications for the prevention and treatment of a range of conditions, including herpes and Guillain-Barre syndrome, which has been linked to the Zika virus.
Many viruses, such as West Nile, Zika, HSV enter the nervous system, where they were thought to be beyond the reach of antibodies. Yale immunobiologists Dr. Akiko Iwasaki and Norifumi Iijima used mice models to investigate how antibodies could gain access to nerve tissue in order to control infection.
In mice infected with herpes, they showed that memory CD4 T cells migrate to the dorsal root ganglia, DRG and spinal cord in response to HSV2. Once inside these neuronal tissues, CD4 T cells secrete interferon-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. ie they reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.
“This is a very elegant design of the immune system to allow antibodies to go to the sites of infection,” said Iwasaki. “The CD4 T cells will only go to the site where there is a virus. It’s a targeted delivery system for antibodies.”
The implications of the finding are multiple. Without CD4 T cells, antibody-based therapies that are being developed for conditions like herpes may not be sufficient to control infection, Iwasaki noted. Conversely, for antibody-mediated autoimmune diseases such as Guillain-Barre, “it may be beneficial to block CD4 from entering the neuronal tissues,” she said.
http://news.yale.edu/2016/05/18/yale-study-how-antibodies-access-neurons-fight-infectionÂ
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17979.html
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