Analysis of the transcriptional program of developing induced regulatory T cells.

CD25+ regulatory T cells develop in the thymus (nTregs), but may
also be generated in the periphery upon stimulation of naive CD4 T
cells under appropriate conditions (iTregs). To gain insight into
the mechanisms governing iTreg development, we performed
longitudinal transcriptional profiling of CD25+ T cells during
their differentiation from uncommitted naive CD4 T cells.
Microarray analysis of mRNA from CD25+ iTregs early after
stimulation revealed expression of genes involved in cell cycle
progression and T cell activation, which largely overlapped with
genes expressed in CD25+ effector T cells (Teffs) used as a
control. Whereas expression of these genes remained elevated in
Teffs, it declined gradually in developing iTregs, resulting in a
more quiescent phenotype in mature iTregs. A similar pattern of
kinetics was observed for biological processes and for
intracellular pathways over-represented within the expressed genes.
A maximum dichotomy of transcriptional activity between iTregs and
Teffs was reached at late stages of their maturation. Of interest,
members of the FoxO and FoxM1 transcription factor family pathways
exhibited a reciprocal expression pattern in iTregs and Teffs,
suggesting a role of these transcription factors in determining T
cell fate.