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Positive Selection by the Pre-TCR Yields Mature CD8⁺ T Cells¹

Yuriko Ito^2,*, Satoko Arai^2,*,, Nicolai S. C. van Oers^*, Iannis Aifantis, Harald von Boehmer and Toru Miyazaki^3,*

^* Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Applied Biological Chemistry, University of Tokyo, Tokyo, Japan; and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115

It has been of much interest whether there is functional redundancy between the constitutively signaling pre-T/TCR (pre-TCR) and ligated TCR complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in -selection at the CD4^-CD8^- double-negative stage and the TCR 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 TCR-deficient (TCR^-/-) mice produced a small number of mature CD8⁺ T cells. Surprisingly, when pre-T 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 TCR^-/- 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-T on a TCR^-/- 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.

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