Tuesday, March 7, 2017

Minimal threshold for Treg repertoire diversity that prevents autoimmunity

If you have read enough of my blog you most likely noticed the preference for research articles that provide some new insight into Tregs' biology.

Few weeks back I analyzed new paper from Rudensky's lab that showed that 50% of mouse with Tregs expressing single TCR specificity were protected from lethal autoimmunity, though not from non-lethal or less lethal forms of  tissue autoimmunity. 

So what is the minimal Tregs TCRβ repertoire diversity required to suppress autoreactive T cells that escape thymic selection?

New paper from Thomas Malek's lab tried to found it out by serially transferring WT Tregs into Treg-deficient IL-2RβKO mice (1st and 2nd level recipients) and analyzing TCR repertoire pre and post transfer. They observed that after each transfer into IL-2RβKO Tregs TCR repertoire diversity got narrower and when it fell < 7000 unique Treg clonal specificity mice showed autoimmunity.

This threshold also correlated with pathological increase in CD62LlowCD44hi population that represents activated T cells typical to autoimmunity.

In summary, this study indicates that there is a minimal threshold for Tregs repertoire diversity that is essential to prevent non-lethal forms of autoimmunity.

David Usharauli

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