Research: the start of Inflammation

Epub: Lodygin et al. A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity. Nat Med. 2013 Apr 28. doi: 10.1038/nm.3182.

Background: MS is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. 

Methods: Here we combined fluorescently labelled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for  imaging of T cell activation. 

Results: In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with meningeal (outer edge of the CNS tissue)  phagocytes. During established disease, the activation process is extended to the depth of the CNS parenchyma (inside the CNS tissue), where the cells form contacts with microglia and recruited phagocytes. 

Conclusions: We show that it is the activation processes during the preclinical phase rather than during established disease that are essential for the intensity and duration of the disease bout.

Sexy science. This study looks at when and where T cells are activated. They make fluorescent molecules (dyes) on signalling factors so when activation occurs the cells glow so they can be imaged. This study suggest the activation process starts at the edge of the spinal cord (in rodents) and moves inwards. They show the more activation that occurs the worse the disease is…is this surprising?

If you asked me this question a few weeks ago I may have said this any way based on staining studies done in the past. 

Science works in spirals layering new information on top of old stuff….hopefully not ignoring the old stuff…….sometimes it re-invents the wheel.

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