Adaptive human regulatory T cells: myth or reality?

It is now well established that a distinct subset of T lymphocytes is essential for downregulating immune responses to both endogenous (self) and exogenous antigens. These Tregs are CD4+ and express high levels of CD25 (the alpha chain of the IL-2 receptor) and the transcription factor Foxp3. The mechanisms determining the lifespan, homeostasis, and in vivo generation of these Tregs are still ill defined. A study by Vukmanovic-Stejic et al. in this issue of the JCI shows that in humans, Tregs are present throughout life but that despite their high throughput, they are short lived (see the related article beginning on page 2423). It is thus unlikely that all CD4+ CD25hi Foxp3+ Tregs are generated as a separate lineage in the thymus. The authors propose that during adulthood, Tregs essentially emerge at the periphery from the memory T cell pool.