EVIDENCE FOR LINEAGE COMMITMENT AND INITIATION OF POSITIVE SELECTION BY THYMOCYTES WITH INTERMEDIATE SURFACE PHENOTYPES

Previous studies have shown that both MHC class I and class II molecul es can stimulate CD4(+)CD8(+) thymocytes to develop into TCR(int) cell s with surface phenotypes, suggesting initial differentiation along ei ther the CD4 or CD8 developmental pathways. In accord with the view th at these cells have undergone lineage commitment, we show here that CD 4(int)TCR(int) cells generated by recognition of either MHC class show the same partial dawn-regulation of CD8 from the level on precursor d ouble positive thymocytes as do almost mature CD4(int)TCR(high) cells positively selected only by MHC class I recognition. As expected of ce lls undergoing positive selection, we find that either class I or clas s II MHC molecules on radioresistant thymic stromal cells alone are su fficient for generation of both types of transitional phenotype cells, Biases in V beta representation associated with allele-dependent posi tive selection are seen only in the TCR(high) and not the TCR(int) coh orts, however. These findings are consistent with the hypothesis that transitional phenotype thymocytes have begun but not completed positiv e selection, and that entry into the CD4 vs CD8 pathways is not unique ly determined by the specific coreceptor-MHC molecule interaction invo lved in precursor thymocyte activation.