Cell expansion and growth arrest phases during the transition from precursor (CD4-8-) to immature (CD4+8+) thymocytes in normal and genetically modified mice.
T cell early precursors belong to the CD3-CD4-CD8- triple negative (TN) thymocyte population that can be subdivided on the basis of CD44, CD25, and heat-stable Ag (HSA) expression. The kinetics and precursor product relationships of these subsets, as well as of the CD4/8low intermediates, were studied by using pulse labeling with bromodeoxyuridine (BrdUrd). The highest frequencies of DNA-synthesizing cells were found in CD44+CD25+ and CD44-CD25low or CD25- subsets. The major TN cell type (CD44-CD25high), as well as CD44+ CD25-HSAlow early precursors, contained a majority of resting cells. RAG-2-/- mice contained less cells in DNA synthesis than normal mice, and CD44-CD25-/low cells were absent. In female mice transgenic for the anti-HYTCR, CD44-CD25high cells were almost all cycling, but a high percentage of resting cells was found in CD44-CD25- cells. In days following the BrdUrd pulse, there was a reduction in the number of BrdUrd+ cells in most subsets, with the exception of the labeled CD44-CD25high cells that showed a bell-shaped curve. The kinetics and 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-CD25high stage involved all cells. In TCR transgenic (Tg) mice, no block was seen at the CD44-CD25high stage, suggesting that early expression of a complete TCR receptor precludes the normal selection step. However, another block in the differentiation process was observed at the CD44-CD25- step in TCR Tg mice, suggesting an additional selection point.
Pénit
C
C
INSERM U345, Necker Institute, Medical Faculty, Necker-Enfants Malades (René Descartes University), Paris, France.
Lucas
B
B
Vasseur
F
F
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002453:Cell Cycle / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004261:DNA Replication / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006182:H-Y Antigen / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D006182:H-Y Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta