Re-inventing the Wheel with Modern Technology

Epub: Pesic et al. 2-photon imaging of phagocyte-mediated T cell activation in the CNS. J Clin Invest. 2013; 123:1192-201. 
doi: 10.1172/JCI67233.

Background: Autoreactive T cells can infiltrate the CNS to cause disorders such as multiple sclerosis. 

Objective & Methods: In order to visualize T cell activation in the CNS, we introduced a truncated fluorescent derivative of nuclear factor of activated T cells (NFAT) as a real-time T cell activation indicator. 

Results: In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, we tracked T cells interacting with structures of the vascular blood-brain barrier (BBB). 2-photon imaging documented the cytoplasmic-nuclear translocation of fluorescent NFAT, indicative of calcium-dependent activation of the T cells in the perivascular space, but not within the vascular lumen. The activation was related to contacts with the local antigen-presenting phagocytes and was noted only in T cells with a high pathogenic potential. T cell activation implied the presentation of an autoantigen, as the weakly pathogenic T cells, which remained silent in the untreated hosts, were activated upon instillation of exogenous autoantigen. Activation did not cogently signal long-lasting arrest, as individual T cells were able to sequentially contact fresh APCs. 

Conclusions: We propose that the presentation of local autoantigen by BBB-associated APCs provides stimuli that guide autoimmune T cells to the CNS destination, enabling them to attack the target tissue.

For many years I have thought that if T cells are activated to cause CNS autoimmunity, then they must see their target in the CNS. With modern technology you can see this happen in real time. We have talked about 2-photon microscopy before and how it is used to visualise things in real time. Check out the videos in this open source paper. They say that antigen-presenting cells in the CNS are important for the development of CNS-autoimmunity.

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  • Hopefully this isn't too unrelated, but at some point in the future would you mind explaining how auto-immunity is plausible. My lack of understanding is in the fact that once our immune system decides it doesn't like something, my impression was that it would fight it to the death very quickly, sometimes even to the extent that it will kill the human for trying so hard.

    My impression is _not_ that the immune system takes its time, sometimes attacking sometimes not, over the period of 40+ years. Is there a behavior mode of the immune system that matches the behavior we see in MS if there is auto-immunity happening?

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