A major role for XXXX in regulatory T cell homeostasis.

@entity2047 @entity19 @entity15592 @entity35185 @entity281 @entity1961
We have previously shown that regulatory T cells (Treg) accumulate dramatically in aged animals and negatively impact the ability to control persistent @entity281 . However, the mechanisms underlying the age-dependent accrual of Treg remain unclear. In this study, we show that Treg accumulation with age is progressive and likely not the result of increased thymic output, increased peripheral proliferation, or from enhanced peripheral conversion. Instead, we found that Treg from aged @entity19 are more resistant to apoptosis than Treg from young @entity19 . Although Treg from aged @entity19 had increased expression of functional @entity15592 , we found that @entity15592 signaling was not required for maintenance of Treg in vivo. Notably, aged Treg exhibit decreased expression of the proapoptotic molecule @entity35185 compared with Treg from young @entity19 . Furthermore, in the absence of @entity35185 , Treg accumulate rapidly, accounting for >25% of the @entity1961 (+) T cell compartment by 6 mo of age. Additionally, accumulation of Treg in @entity35185 -deficient @entity19 occurred after the cells left the transitional recent thymic emigrant compartment. Mechanistically, we show that @entity2047 drives preferential proliferation and accumulation of @entity35185 (lo) Treg. Collectively, our data suggest that chronic stimulation by @entity2047 leads to preferential expansion of Treg having low expression of @entity35185 , which favors their survival and accumulation in aged hosts.
