Dynamic expression of T-bet and GATA3 by regulatory T cells maintains immune tolerance

Regulatory T (T(reg)) cells can express the transcription factors T-bet and GATA3 but the function of this expression and whether such cells represent stable subsets is still unknown. By using multiple reporter tools, we show that the expression of T-bet and GATA3 in T(reg) cells is dynamically influenced by the cytokine environment. T(reg) cell-specific deletion of either Tbx21 or Gata3 genes singly did not result in loss of T(reg) cell functions; however, mice with combined deficiency of both genes in T(reg) cells developed severe autoimmune-like diseases. Loss of T(reg) cell function was correlated with RORγt transcription factor upregulation and reduced Foxp3 expression. Thus, in the steady state, activated T(reg) cells transiently upregulate either T-bet or GATA3 to maintain T cell homeostasis.