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Publication : β-Selection-induced proliferation is required for αβ T cell differentiation.

First Author  Kreslavsky T Year  2012
Journal  Immunity Volume  37
Issue  5 Pages  840-53
PubMed ID  23159226 Mgi Jnum  J:190441
Mgi Id  MGI:5448870 Doi  10.1016/j.immuni.2012.08.020
Citation  Kreslavsky T, et al. (2012) beta-Selection-induced proliferation is required for alphabeta T cell differentiation. Immunity 37(5):840-53
abstractText  Proliferation and differentiation are tightly coordinated to produce an appropriate number of differentiated cells and often exhibit an antagonistic relationship. Developing T cells, which arise in the thymus from a minute number of bone-marrow-derived progenitors, undergo a major expansion upon pre-T cell receptor (TCR) expression. The burst of proliferation coincides with differentiation toward the alphabeta T cell lineage-but the two processes were previously thought to be independent from one another, although both were driven by signaling from pre-TCR and Notch receptors. Here we report that proliferation at this step was not only absolutely required for differentiation but also that its ectopic activation was sufficient to substantially rescue differentiation in the absence of Notch signaling. Consistently, pharmacological inhibition of the cell cycle machinery also blocked differentiation in vivo. Thus the proliferation step is strictly required prior to differentiation of immature thymocytes.
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