Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene.
The diversity of the T cell receptor repertoire is generated by rearrangement of gene elements in immature thymocytes. To identify a thymic signal that induces this rearrangement, a variety of agents were tested for their ability to induce rearrangement of the T cell receptor beta gene in suspensions of thymocytes from mouse embryos at day 14 of gestation. Of 16 agents tested, only interleukin-7 (IL-7) induced V(D)J gene rearrangement and sustained expression of the RAG-1 and RAG-2 genes, which are known to control rearrangement. These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development.
Muegge
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K
Biological Carcinogenesis and Development Program, Program Resources Inc./Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.
Vila
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Durum
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016654:Genes, RAG-1; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D011506:Proteins / Q000235:genetics; D019089:Stem Cell Factor; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D015851:Interleukin-7; D011506:Proteins; C499308:Rag2 protein, mouse; D019089:Stem Cell Factor; C064655:V(D)J recombination activating protein 2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate