CD8 lineage commitment in the absence of CD8.

The absence of cytotoxic T lymphocyte activity and the failure of MHC class I-restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8alpha-deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We report that variants of the antigenic peptide that delete TCR transgenic thymocytes from CD8 wild-type but not CD8alpha-deficient mice can restore positive selection of CD8 lineage cells in the absence of CD8. The positively selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic peptide, and express CD8beta mRNA. Interestingly, there was no enhanced selection of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of CD8, provided instructive signaling for commitment to the CD8 lineage. Our results are discussed in terms of recent models of T cell lineage commitment.