Redefining Privileges: The brain and the immune system

For this week’s throwback, lets take a look at a paper1 by Corriveau et al. that redefined the popular view that the central nervous system (CNS) is “immune-privileged”.

Figure from Boulanger and Shatz (2004) showing the presence of three MHC class 1 molecules' mRNA in the mouse brain

Figure from Boulanger and Shatz (2004) showing the presence of three MHC class 1 molecules' mRNA in the mouse brain

The CNS was thought to be immune-privileged due to its diminished immune response and its blood brain barrier-mediated isolation from the immune system2. As a result, molecules associated with the immune system were considered to be absent in the CNS. This belief was further supported by numerous studies that failed to detect the presence of immune molecules in neurons. In the 90s, studies began to be published describing evidence that neurons do indeed express immune molecules following injury or stress3. Remarkably, Corriveau et al. demonstrate that healthy, uninjured neurons also express immune molecules, specifically the MHC class 1 molecules. This was a notion that was initially met with skepticism.

So why did others fail to detect the presence of these molecules? The authors offer a few possible explanations in this paper: 1) They were not looking in the right place at the right time; and 2) A more sensitive detection method was used in the Corriveau et al. paper.

“...we got a nice note back telling us we must have made some fundamental mistake in our lab,” Shatz recalls. But she wasn’t deterred. “I told the guys in my lab not to get discouraged,” she says. “I knew we weren’t wrong.”

From http://gruber.yale.edu/neuroscience/carla-shatz

Another interesting piece of data presented by Corriveau et al. was that the more active the neuronal network, the greater the expression of these MHC class 1 molecules. This data when combined with the earlier data showing presence of these molecules in healthy neurons led the authors to speculate that immune molecules may be involved in non-immunological roles in the nervous system. And they were right! Many papers since have demonstrated roles for MHC class 1 molecules in various roles primarily involving the fine-tuning of neuronal connections in the developing brain5. Furthermore, irregularities in immune protein function have been implicated in numerous neurological disorders. Corriveau et al. definitely played a huge role in revamping the field of neuroimmunology and has since opened up novel ways of thinking about brain development and disease.

Reference:

  1. Corriveau R.A., Huh, G.S., Shatz, C.J. (1998) Regulation of Class 1 MHC gene expression in the developing and mature CNS by neural activity. Neuron Vol. 21, 505-520
  2. Carson, M.J., Doose, J.M., Melchior, B., Schmid, C.D., Ploix, C.C. (2009) CNS immune privilege: hiding in plain sight. Immunol Reev. 213:48-65
  3. Boulanger, L.M., Shatz, C.J. (2004) Immune signaling in neural development, synaptic plasticity and disease. Nature Reviews Neuroscience
  4. http://gruber.yale.edu/neuroscience/carla-shatz
  5. Shatz, C.J. MHC Class 1: An unexpected role in neuronal plasticity (2009) Neuron 64