Anderson Stephen J, Lauritsen Jens Peter Holst, Hartman Matthew G, Foushee Ann Marie Digeorge, Lefebvre Juliette M, Shinton Susan A, Gerhardt Brenda, Hardy Richard R, Oravecz Tamas, Wiest David L
Division of Immunology and Hematology, Lexicon Genetics, Inc., 8800 Technology Forest Place, The Woodlands, TX 77381, USA.
Immunity. 2007 Jun;26(6):759-72. doi: 10.1016/j.immuni.2007.04.012. Epub 2007 Jun 7.
The alphabeta and gammadelta T lineages are thought to arise from a common precursor; however, the regulation of separation and development of these lineages is not fully understood. We report here that development of alphabeta and gammadelta precursors was differentially affected by elimination of ribosomal protein L22 (Rpl22), which is ubiquitously expressed but not essential for translation. Rpl22 deficiency selectively arrested development of alphabeta-lineage T cells at the beta-selection checkpoint by inducing their death. The death was caused by induction of p53 expression, because p53 deficiency blocked death and restored development of Rpl22-deficient thymocytes. Importantly, Rpl22 deficiency led to selective upregulation of p53 in alphabeta-lineage thymocytes, at least in part by increasing p53 synthesis. Taken together, these data indicate that Rpl22 deficiency activated a p53-dependent checkpoint that produced a remarkably selective block in alphabeta T cell development but spared gammadelta-lineage cells, suggesting that some ribosomal proteins may perform cell-type-specific or stage-specific functions.
αβ和γδ T细胞谱系被认为起源于一个共同的前体细胞；然而，这些谱系的分离和发育调控尚未完全明确。我们在此报告，αβ和γδ前体细胞的发育受到核糖体蛋白L22（Rpl22）缺失的不同影响，Rpl22在全身表达，但对翻译并非必需。Rpl22缺陷通过诱导αβ谱系T细胞死亡，在β选择检查点选择性地阻止其发育。这种死亡是由p53表达的诱导引起的，因为p53缺陷可阻止死亡并恢复Rpl22缺陷胸腺细胞的发育。重要的是，Rpl22缺陷导致αβ谱系胸腺细胞中p53选择性上调，至少部分是通过增加p53合成。综上所述，这些数据表明，Rpl22缺陷激活了一个p53依赖的检查点，该检查点在αβ T细胞发育中产生了显著的选择性阻滞，但γδ谱系细胞未受影响，这表明一些核糖体蛋白可能具有细胞类型特异性或阶段特异性功能。
