The effect of constitutive CD8 expression on thymic selection; implications for the mechanism of CD4 and CD8 lineage...

The choice of an immature T cell to become a CD4 cell or a CD8 cell may be the result of instructive signals generated during positive selection. Alternatively, the initial commitment to a CD4 or CD8 lineage may be made independently of the specificity of the TCR. In this article, I describe our efforts to test the latter possibility using mice expressing a constitutive CD8 transgene. If lineage commitment is initially independent of MHC specificity, expression of ectopic CD8 in CD4 cells should allow CD4 cells with class I specific TCR to mature. We find that although some mature class I specific CD4 cells can be detected in CD8 transgenic mice, they are a minor population compared to class I selected CD8 cells. The implications of these results for the mechanism of lineage commitment are discussed.