Ikaros is required to survive positive selection and to maintain clonal diversity during T-cell development in the thymus.

ABSTRACT: The zinc-finger protein Ikaros is a key player in T-cell development and a potent tumor suppressor in thymocytes. To understand the molecular basis of its function, we disabled Ikaros activity in vivo using a dominant negative Ikaros transgene (DN-IkTg). In DN-IkTg mice, T-cell development was severely suppressed, and positively selected thymocytes clonally expanded, resulting in a small thymus with a heavily skewed T-cell receptor (TCR) repertoire. Notably, DN-IkTg induced vigorous proliferation concomitant to downregulation of antiapoptotic factor expression such as Bcl2. Ikaros activity was required during positive selection, and specifically at the CD4(+)CD8(lo) intermediate stage of thymocyte differentiation, where it prevented persistent TCR signals from inducing aberrant proliferati

SUBMITTER: Tinsley KW 

PROVIDER: S-EPMC3790506 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature