Unequal Contribution of Akt Isoforms in the Double-Negative to Double-Positive Thymocyte Transition

Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition.

Pre-TCR signals regulate the transition of the double-negative (DN) 3 thymocytes to the DN4, and subsequently to the double-positive (DP) stage. In this study, we show that pre-TCR signals activate Akt and that pharmacological inhibition of the PI3K/Akt pathway, or combined ablation of Akt1 and Akt2, and to a lesser extent Akt1 and Akt3, interfere with the differentiation of DN3 and the accumul...

The MAP Kinase Pathway Controls Differentiation from Double-Negative to Double-Positive Thymocyte

T cell development is regulated at two major control points where maturation, proliferation, and antigen receptor gene rearrangement are coordinated. Progression through these developmental control points is dependent upon the expression of different forms of the T cell receptor. Here we show that the MAP kinase cascade is a regulator of the differentiation of immature thymocytes from double-ne...

Double - Negative 3 to Double - Positive Stages

Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte

In the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self-antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single-positive (SP) thymocyte ratio. Here, we ...

Surface expression of Notch1 on thymocytes: correlation with the double-negative to double-positive transition.

Notch1 plays a critical role in regulating T lineage commitment during the differentiation of lymphoid precursors. The physiological relevance of Notch1 signaling during subsequent stages of T cell differentiation has been more controversial. This is due in part to conflicting data from studies examining the overexpression or targeted deletion of Notch1 and to difficulties in distinguishing bet...