The pretcr-dependent dn3 to dp transition requires notch signaling, is improved by cxcl12 signaling and is inhibited by il-7 signaling
Rolink, Antonius G.
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Tussiwand, Roxane; Engdahl, Corinne; Gehre, Nadine; Bosco, Nabil; Ceredig, Rod; Rolink, Antonius G. (2011). The pretcr-dependent dn3 to dp transition requires notch signaling, is improved by cxcl12 signaling and is inhibited by il-7 signaling. European Journal of Immunology 41 (11), 3371-3380
The requirement for Notch signaling during T-cell development has been extensively studied. Nevertheless, the developmental stage at which it is required and whether additional signaling pathways are needed are still poorly understood. By using a stromal-cell-free culture system, we show that sorted double-negative 3 (DN3) thymocytes only require a Delta-like-4-induced Notch signal to differentiate into double-positive (DP) cells. This differentiation process is preTCR-alpha dependent. DN3 cells undergo 4-5 proliferation cycles, and the addition of the chemokine CXCL12 improves proliferation. IL-7 blocks the differentiation of DN3 cells to DP cells but not the Notch-induced proliferation of cultured DN3 cells. The impaired differentiation correlates with an inhibition of Rag-2 up-regulation. Overall, the in vitro stromal-cell-free culture system presented here also provides a powerful and unique tool for studying the mechanisms involved in the positive and negative selection of T cells.