MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent

The generation of mature CD4 T cells from CD4(+)CD8(+) precursor thymocytes usually requires corecognition of class II MHC by a TCR and CD4, while the production of mature CD8 T cells requires corecognition of class I MHC by a TCR and CD8. To assess the role of the CD4 coreceptor in development and lineage commitment, we generated CD4-deficient mice expressing a transgenic class Ii-specific TCR. Surprisingly, in the absence of CD4 a large number of T cells mature, but these cells appear in the CD8 lineage. Thus, when CD4 is present, the majority of immature T cells with this class Ii-specific TCR choose the CD4 lineage but develop in the CD8 pathway when CD4 is absent. The results indicate that even for TCRs that are not dependent on coreceptor for MHC recognition, the coreceptor can influence the lineage choice. These findings are considered in terms of a quantitative signaling model for CD4/CD8 lineage commitment.