It has been of much interest whether there is functional redundancy between the constitutively signaling pre-Tα/TCRβ (pre-TCR) and ligated TCRαβ complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in β-selection at the CD4-CD8- double-negative stage and the TCRαβ being crucial for positive/negative selection at the CD4+CD8+ double-positive stage. We found that the pre-TCR expressed on double-positive cells in TCRα-deficient (TCRα-/-) mice produced a small number of mature CD8+ T cells. Surprisingly, when pre-Tα was overexpressed, resulting in augmentation of pre-TCR expression, there was a striking increase of the CD8+ T cells. In addition, even in the absence of up-regulation of pre-TCR expression, a similar increase of CD8+ T cells was also observed in TCRα-/- mice overexpressing Egr-1, which lowers the threshold of signal strength required for positive selection. In sharp contrast, the CD8+ T cells drastically decreased in the absence of pre-Tα on a TCRα-/- background. Thus, the pre-TCR appears to functionally promote positive selection of CD8+ T cells. The biased production of CD8+ T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment.
ASJC Scopus subject areas
- Immunology and Allergy