Tbt-1, a new T-box transcription factor induced in activated Th1 and CD8(+) T cells

Differentiation of CD4(+) T cells into T helper (Th) 1 or Th2 cells require s the cytokines interleukin (IL)-12 and IL-4, respectively. However, transc ription factors that regulate expression of Th1 or Th2 cell-specific genes remain largely unclear. In the present study, a new Th1-specific transcript ion factor, named Tbt-1 (T-box protein expressed in T lymphocytes), was ide ntified. Tbt-1 is a novel member of the T-box family, which is characterize d by a conserved T-box DNA-binding domain. Unlike other known T-box protein s that regulate embryo development and organogenesis, Tbt-1 expression is r estricted to adult lymphoid organs. Tbt-1 mRNA is only detected in peripher al lymphoid tissues such as spleen, lymph nodes, and blood leukocytes, but not in thymus or bone marrow. Tbt-1 mRNA is not detected in resting T cells but is strongly induced in differentiating Th1 cells and CD8(+) cytotoxic effector cells. In contrast, Tbt-1 expression was not observed in the entir e process of Th2 cell differentiation. In addition, phylogenetic analyses i ndicate that Tbt-1 co-evolved with adaptive immune responses. Thus, Tbt-1 i s the first T-box transcription factor shown to be specific for Th1 cell di fferentiation.