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
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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