CELL EXPANSION AND GROWTH ARREST PHASES DURING THE TRANSITION FROM PRECURSOR (CD4(-)8(-)) TO IMMATURE (CD4(-MODIFIED MICE()8(+)) THYMOCYTESIN NORMAL AND GENETICALLY)

T cell early precursors belong to the CD3(-)CD4(-)CD8(-) triple negati ve (TN) thymocyte population that can be subdivided on the basis of CD 44, CD25, and heat-stable Ag (HSA) expression. The kinetics and precur sor product relationships of these subsets, as well as of the CD4/8(lo w) intermediates, were studied by using pulse labeling with bromodeoxy uridine (BrdUrd). The highest frequencies of DNA-synthesizing cells we re found in CD44(+)CD25(+) and CD44(-)CD25(low) or CD25(-) subsets. Th e major TN cell type (CD44(-)CD25(high)), as well as CD44(+)CD25(-)HSA (low) early precursors, contained a majority of resting cells. RAG-2(- /-) mice contained less cells in DNA synthesis than normal mice, and C D44(-)CD25(-low) cells were absent. In female mice transgenic for the anti-HY TCR, CD44(-)CD25(high) cells were almost all cycling, but a hi gh percentage of resting cells was found in CD44(-)CD25(-) cells. In d ays following the BrdUrd pulse, there was a reduction in the number of BrdUrd(+) cells in most subsets, with the exception of the labeled CD 44(-)CD25(high) cells that showed a bell-shaped curve. The kinetics an d cell size evolution suggest that the majority of these cells do not give rise to CD4(+)CD8(+) cells. In RAG-2(-/-) cells, the block at the CD44(-)CD25(high) stage involved ail cells. In TCR transgenic (Tg) mi ce, no block was seen at the CD44(-)CD25(high) stage, suggesting that early expression of a complete TCR receptor precludes the normal selec tion step. However, another block in the differentiation process was o bserved at the CD44(-)CD25(-) step in TCR Tg mice, suggesting an addit ional selection point.