Evidence for lineage commitment and initiation of positive selection by thymocytes with intermediate surface phenotypes.

Abstract

Previous studies have shown that both MHC class I and class II molecules can stimulate CD4+CD8+ thymocytes to develop into TCRint cells with surface phenotypes, suggesting initial differentiation along either the CD4 or CD8 developmental pathways. In accord with the view that these cells have undergone lineage commitment, we show here that CD4intTCRint cells generated by recognition of either MHC class show the same partial down-regulation of CD8 from the level on precursor double positive thymocytes as do almost mature CD4intTCRhigh cells positively selected only by MHC class I recognition. As expected of cells undergoing positive selection, we find that either class I or class II MHC molecules on radioresistant thymic stromal cells alone are sufficient for generation of both types of transitional phenotype cells. Biases in V beta representation associated with allele-dependent positive selection are seen only in the TCRhigh and not the TCRint cohorts, however. These findings are consistent with the hypothesis that transitional phenotype thymocytes have begun but not completed positive selection, and that entry into the CD4 vs CD8 pathways is not uniquely determined by the specific coreceptor-MHC molecule interaction involved in precursor thymocyte activation.