Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros
- Author(s)
- Winandy, S; Wu, L; Wang, JH; Georgopoulos, K;
- Details
- Publication Year 1999-10-18,Volume 190,Issue #8,Page 1039-1048
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- T cell differentiation relies on pre-T cell receptor (TCR) and TCR signaling events that take place at successive steps of the pathway. Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without expression of a pre-TCR complex. Subsequent events in T cell development mediated by TCR involving transition from the double positive to the single positive stage are also regulated by Ikaros. Nonetheless, ill Ikaros-deficient thymocytes, the requirement of pre-TCR expression for expansion of immature thymocytes as they progress to the double positive stage is still maintained, and the T cell malignancies that invariably arise in the thymus of Ikaros-deficient mice are dependent on either pre-TCR or TCR signaling. We conclude that Ikaros regulates T cell differentiation, selection, and homeostasis by providing signaling thresholds for pre-TCR and TCR.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- GENE REARRANGEMENT; NEGATIVE SELECTION; BETA-CHAIN; MICE; EXPRESSION; LYMPHOCYTES; THYMOCYTES; MUTATION; THYMUS
- Publisher's Version
- https://doi.org/10.1084/jem.190.8.1039
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-10-18 12:00:00