Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance

Regulatory T cells (T-reg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in T-reg cells was dynamically influenced by the cytokine environment. T-reg cell-specific deletion of the gene encoding either T-bet (Tbx21) or GATA-3 (Gata3) alone did not result in loss of T-reg cell function; however, mice with combined deficiency in both genes in T-reg cells developed severe autoimmune-like diseases. Loss of T-reg cell function correlated with upregulation of expression of the transcription factor ROR gamma t and reduced expression of the transcription factor Foxp3. Thus, in the steady state, activated T-reg cells transiently upregulated either T-bet or GATA-3 to maintain T cell homeostasis.