Soloff R S, Wang T G, Dempsey D, Jennings S R, Wolcott R M, Chervenak R
Department of Microbiology and Immunology, Louisiana State University Medical Center, and The Biomedical Research Institute of Northwest Louisiana, Shreveport, 71130, USA.
Mol Immunol. 1997 Apr;34(6):453-62. doi: 10.1016/s0161-5890(97)00051-5.
Rearrangement of the T cell antigen receptor genes is a complex, highly regulated process. To gain a better understanding of the extracellular factors involved in the regulation of TCR beta and gamma gene rearrangement in adult murine bone marrow-resident precursor T cells, several cytokines were tested for their ability to induce gene recombination. A selected population of C58/J bone marrow cells (Thy 1(low), CD3, CD8, B220) that is enriched for pre-T cell activity was propagated in vitro in medium supplemented with IL-3 and mast cell growth factor (MGF, also referred to as stem cell factor, Steele factor and c-kit ligand). These cytokines were required for the maintenance of pre-T cell activity in culture, but had no effect on TCR gene expression. Several additional cytokines were added to the culture medium. Of all those tested, only IL-7 induced complete rearrangement of the TCR gamma locus. Complete rearrangement of the TCR beta locus was not induced under any of the culture conditions analysed here. The bone marrow cells cultured in IL-3, MGF and IL-7 did not begin to express mature T cell proteins and maintained their in vivo progenitor potential. Furthermore, IL-7 cultured bone marrow cells were capable of differentiation in vivo into all phenotypic subpopulations of T cells, without an apparent bias toward the gammadelta lineage. The data presented here suggest that TCR gamma gene rearrangement in adult pre-T cells is regulated by IL-7, but that the TCR beta locus requires additional or alternative signals for the induction of complete rearrangement.
T细胞抗原受体基因的重排是一个复杂且受到高度调控的过程。为了更好地理解参与成年小鼠骨髓驻留前体T细胞中TCRβ和γ基因重排调控的细胞外因子，对几种细胞因子诱导基因重组的能力进行了测试。选择了一群富含前体T细胞活性的C58/J骨髓细胞（Thy 1(低)、CD3、CD8、B220），在补充有IL-3和肥大细胞生长因子（MGF，也称为干细胞因子、Steel因子和c-kit配体）的培养基中进行体外培养。这些细胞因子是维持培养中前体T细胞活性所必需的，但对TCR基因表达没有影响。向培养基中添加了几种其他细胞因子。在所有测试的细胞因子中，只有IL-7能诱导TCRγ基因座的完全重排。在此处分析的任何培养条件下，均未诱导TCRβ基因座的完全重排。在IL-3、MGF和IL-7中培养的骨髓细胞并未开始表达成熟T细胞蛋白，并维持了它们在体内的祖细胞潜能。此外，在IL-7中培养的骨髓细胞能够在体内分化为T细胞的所有表型亚群，而没有明显偏向γδ谱系。此处呈现的数据表明，成年前体T细胞中的TCRγ基因重排受IL-7调控，但TCRβ基因座需要额外的或替代的信号来诱导完全重排。
