You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Abstract
To investigate the temporal regulation of the commitment of immature thymocytes to either the CD4+ or the CD8+ lineage in the thymus, we developed a transgenic mouse that expressed a tetracycline-inducible gene encoding the tyrosine kinase ζ chain–associated protein kinase of 70 kD (Zap70), which restored development in Zap70−/− thymocytes arrested at the preselection, CD4+CD8+ double-positive (DP) stage. After induction of the expression of Zap70 and the production of Zap70 protein, CD4+ single-positive (SP) cells that expressed Zbtb7b (which encodes the CD4+ T cell–associated transcription factor ThPOK) became abundant within 30 hours, whereas CD8+ SP cells were not detectable until day 4. We found that mature CD4+ and CD8+ cells arose from phenotypically distinct subsets of DP thymocytes that developed with different kinetics and contrasting sensitivities to stimulation of the T cell antigen receptor (TCR). In wild-type mice, expression of endogenous Zap70 progressively increased during maturation of the DP subsets, and the abundance of Zap70 protein determined the sensitivity of the cells to stimulation of the TCR. This temporal gradient in the amount of Zap70 protein enabled the selection of CD4+ and CD8+ repertoires in separate temporal windows and at different TCR signaling thresholds, thereby facilitating discrimination of distinct positive selection signals in these lineages.