Abstract
Deleterious immune responses that cause autoimmune diseases such as type 1 diabetes are normally kept in check by a myriad of mechanisms. Among these, protection mediated by CD4+Foxp3+ Tregs constitutes an essential pathway. Much work over the past decade aimed to understand how Tregs affect immune responses triggered by effector T cells (Teffs), but less is known about how Teffs affect Tregs. In this issue of the JCI, Grinberg-Bleyer et al. report the clearest example thus far regarding this important aspect of Treg biology. They find that in mice, sustained protection from diabetes by Tregs is dependent on Teffs and partially dependent on TNF-α, a cytokine traditionally considered proinflammatory.