The hidden truth about gene expression in Tregs: is it what you don't see that counts?

A population of IL-10 secreting regulatory T cells (PI-Tregs) can be induced in a mouse TCR transgenic model of experimental autoimmune encephalomyelitis (EAE) by intranasal administration of the N-terminal peptide of myelin basic protein. A paper in this issue of the European Journal of Immunology identifies patterns of gene expression that distinguish PI-Treg from naïve T cells after activation in vivo. PI-Tregs are anergic and the expression of egr2 may be involved in regulation of the cell cycle. The surprising expression of the Th1 determining gene T-bet in PI-Tregs may be functionally relevant as transfection of T-bet into a hybridoma induced some genes associated with regulatory T cells, such as tlr2 and gzmb. In this commentary, PI-Tregs are considered in comparison to other Tregs, such as the natural CD4(+)CD25(+) and Tr1 cells, and there seems to be considerable overlap in gene expression between all three Treg populations, but also with both Th1 and Th2 cells. It is suggested that regulatory activity may be a common feature of all activated T cells and that a defining principle of a Treg is the lack of effector functions due to a partial or incomplete differentiation to either Th1 or Th2.