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 requires the cytokines interleukin (IL)-12 and IL-4, respectively. However, transcription factors that regulate expression of Th1 or Th2 cell-specific genes remain largely unclear. In the present study, a new Th1-specific transcription factor, named Tbt-1 (T-box protein expressed in T lymphocytes), was identified. Tbt-1 is a novel member of the T-box family, which is characterized by a conserved T-box DNA-binding domain. Unlike other known T-box proteins that regulate embryo development and organogenesis, Tbt-1 expression is restricted to adult lymphoid organs. Tbt-1 mRNA is only detected in peripheral 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 Thl cells and CD8+ cytotoxic effector cells. In contrast, Tbt-1 expression was not observed in the entire process of Th2 cell differentiation. In addition, phylogenetic analyses indicate that Tbt-1 co-evolved with adaptive immune responses. Thus, Tbt-1 is the first T-box transcription factor shown to be specific for Th1 cell differentiation.
Shier
P
P
The RW Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Hofstra
C L
CL
Ma
X J
XJ
Wu
Y
Y
Ngo
K
K
Fung-Leung
W P
WP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D013154:Spleen / Q000166:cytology; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000145:classification / Q000235:genetics*; D000098815:T-bet Transcription Factor
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D003208:Concanavalin A