Preselection CD4+CD8+ thymocytes modulate TCR responsiveness following TCRβ selection

Modulation of T cell receptor (TCR) sensitivity during positive selection is critical to avoid negative selection and direct thymocytes into their appropriate lineage. Thymocytes just prior to positive selection (preselection) are highly responsive to low affinity self-ligands and are also actively rearranging their TCRα locus as they await a positive selection signal. Preselection double-positive thymocytes were thought to be relatively homogeneous, and TCR modulation during this stage had not been previously described. Here, we provide evidence for progressive gene expression changes within the preselection double-positive thymocyte population that correlates with a gradual reduction in TCR responsiveness and reduced upregulation of TCR target genes associated with the CD4 fate. We relate these observations to the link between positive selection and T cell lineage commitment.