Regulatory T cells (TREG cells) are required to maintain tolerance to self and maybe even to foreign antigens, such as commensal bacteria-derived antigens. But how exactly TREG cells keep other immune cells in check is not clear.
Simply speaking, paradox with TREG cells is that if TREG cells are too potent or constantly "active" then they should prevent any immune response to any antigens. If TREG cells are not constantly "active", then what signal(s) activate them? and if active TREG cells are "inhibited" by infection and they regain their inhibitory functions once infection is cleared, how is such system coordinated? Basically, none of the available models can satisfactorily explain full spectrum of TREG cells biology. Hence the reason why translation of basic knowledge about TREG cells for clinical application is so slow.
So, every time we see new paper about TREG cells we hope that we can acquire "some" missing information. In this regards, lets examine new paper in Science from Harvey Cantor's lab. There, the authors found that presence of transcription factor Helios is necessary to stabilize TREG cells phenotype.
This is a simple, observation-type paper. Initially, the authors showed that starting from 5 months of age, mice deficient for Helios develop auto-antibodies to self antigens.
Next, using adoptive transfer experiments in combination with bone marrow chimera, the authors showed that Helios-deficient TREG cells lacked suppressive function.
Finally, the authors showed that Helios-deficient TREG cells displayed unstable phenotype and could be induced to express effector cytokines.
In summary, this study showed that Helios played an important role in stability of TREG cells phenotype, especially during the ageing process. Of note, other studies with Helios-deficient mice did not observe the same phenotype. The authors claim that it has to do with the age difference of the experimental mice used in those earlier experiments. But genetic difference between mice colony itself or their gut flora could not be dismissed without proper experimentation.