ASYNCHRONOUS CORECEPTOR DOWN-REGULATION AFTER POSITIVE THYMIC SELECTION - PROLONGED MAINTENANCE OF THE DOUBLE-POSITIVE STATE IN CD8 LINEAGEDIFFERENTIATION DUE TO SUSTAINED BIOSYNTHESIS OF THE CD4 CORECEPTOR

In several experimental systems analyzing the generation of single pos itive (SP) thymocytes from double positive (DP) thymocytes, CD4 SP cel ls have been shown to appear before CD8 SP cells. This apparent tempor al asymmetry in the maturation of CD4 SP and CD8 SP thymocytes could e ither be due to divergent molecular differentiation programs of the tw o T cell lineages, or merely to slower degradation kinetics of the CD4 protein. To study this question in unmanipulated in vivo differentiat ion, we developed a four-color now cytometry protocol which identifies a recently activated TCR(int)CD69(pos) thymocyte population containin g DP cells and early CD4 SP cells but no CD8 SP cells. We show that th ese TCR(int)D69(pos) thymocytes represent a transitory stage in the ma instream alpha beta T cell lineage. The precursors of the CDS SP cells are contained in this population as incompletely selected DP cells. M oreover, we show that expression of both coreceptors in the TCR(int)CD 69(pos) population depends on transcriptional and translational activi ty, thus excluding differences in turnover rates of the CD4 and CD8 pr oteins as the cause of the asynchrony in differentiation of the CD4 an d CD8 lineages.