Pre–T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros
S Winandy, L Wu, JH Wang… - The Journal of …, 1999 - rupress.org
S Winandy, L Wu, JH Wang, K Georgopoulos
The Journal of experimental medicine, 1999•rupress.orgT 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 …
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 …
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, in 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.
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