LINEAGE COMMITMENT IN THE THYMUS - ONLY THE MOST DIFFERENTIATED (TCR(HI)BCL-2(HI)) SUBSET OF CD4(+)CD8(+) THYMOCYTES HAS SELECTIVELY TERMINATED CD4 OR CD8 SYNTHESIS

Lineage commitment is a developmental process by which individual CD4( +)CD8(+) (double positive, DP) thymocytes make a decision to different iate into either CD4(+) or CD8(+) T cells. However, the molecular even t(s) that defines lineage commitment is controversial. We have previou sly proposed that lineage commitment in DP thymocytes can be molecular ly defined as the selective termination of CD4 or CD8 coreceptor synth esis. The present study supports such a molecular definition by showin g that termination of either CD4 or CD8 synthesis is a highly regulate d event that is only evident within the most differentiated DP subset (CD5(hi)CD69(hi)TCR(hi)bcl-2(hi)). In fact, essentially all cells with in this DP subset actively synthesize only one coreceptor molecule. In addition, the present results identify three distinct subpopulations of DP thymocytes that define the developmental progression of the line age commitment process and demonstrate that lineage commitment is coin cident with upregulation of TCR and bcl-2. Thus, this study supports a molecular definition of lineage commitment and uniquely identifies TC R(hi)bcl-2(hi) DP thymocytes as cells that are already committed to ei ther the CD4 or CD8 T cell lineage.