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.
Characterization of genomic DNA encoding the insulin receptor-related receptor (IRR) previously revealed that the predicted IRR protein is closely related to the insulin and insulin-like growth factor-I receptor protein-tyrosine kinases. Using rat IRR genomic DNA as probe, IRR transcripts were detected by Northern blot analysis in RNA from rat kidney, stomach, and thymus, but not in RNA from other tissues, including skeletal muscle, brain, intestine, and uterus. Primer extension analysis using RNA from stomach revealed a single transcriptional start site 29 basepairs down-stream from a putative TATA box and 544 basepairs up-stream of the initiator methionine codon. Amplification of IRR cDNA by polymerase chain reaction and isolation of partial IRR cDNA clones confirmed that the IRR gene is an expressed gene.
Characterization of genomic DNA encoding the insulin receptor-related receptor (IRR) previously revealed that the predicted IRR protein is closely related to the insulin and insulin-like growth factor-I receptor protein-tyrosine kinases. Using rat IRR genomic DNA as probe, IRR transcripts were detected by Northern blot analysis in RNA from rat kidney, stomach, and thymus, but not in RNA from other tissues, including skeletal muscle, brain, intestine, and uterus. Primer extension analysis using RNA from stomach revealed a single transcriptional start site 29 basepairs down-stream from a putative TATA box and 544 basepairs up-stream of the initiator methionine codon. Amplification of IRR cDNA by polymerase chain reaction and isolation of partial IRR cDNA clones confirmed that the IRR gene is an expressed gene.
DNA encoding the insulin receptor-related receptor (1RR), a novel receptor whose predicted primary structure is similar to those of the insulin and insulin-like growth factor I receptors, has been used in Southern blot analysis of DNA from human × mouse somatic cell hybrids to assign the IRR gene (INSRR) to human chromosome 1.
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