What would Treg-cell biology look like when viewed from a rationalized perspective?

The argument that Treg cells play a role in determining the Self (S)-Nonself (NS) discrimination (i.e. tolerance) is challenged based on two theoretical constructs, the two stage-two signal model for the S-NS discrimination and the Tritope model of TCR function. The conclusions are then tested by reinterpreting a published probing set of data purporting to show that Treg cells regulate tolerance. It is concluded that the major role of suppression is to operate as a feedback mechanism modulating the magnitude of the effector response; it is not a determinant of the S-NS discrimination (i.e. tolerance).