Ablation of Ribosomal Protein L22 Selectively Impairs alpha beta T Cell Development by Activation of a p53-Dependent Checkpoint

• Published in: Immunity (Cambridge, Mass.) Vol. 26; no. 6; pp. 759 - 772
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: 01.06.2007
• ISSN: 1074-7613
• DOI: 10.1016/j.immuni.2007.04.012

The alpha beta and gamma delta 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 alpha beta and gamma delta 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 alpha beta -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 alpha beta -lineage thymocytes, at least in part by increasing p53synthesis. Taken together, these data indicate that Rpl22 deficiency activated a p53-dependent checkpoint that produced a remarkably selective block in alpha beta T cell development but spared gamma delta -lineage cells, suggesting that some ribosomal proteins may perform cell-type-specific or stage-specific functions.