Kinetics of mature T-cell development in the thymus.

TLDR

The study used in vivo [3H]-thymidine labeling, FACS isolation of defined thymocyte subsets, and autoradiographic analysis to reassess the balance of thymocyte birth, maturation, and death. Mature thymocytes (CD4⁺CD8⁻CD3⁺ or CD4⁻CD8⁺CD3⁺) entered the thymus from a small nondividing cortical pool, with little evidence of division after maturation, indicating a one‑for‑one differentiation and limited negative selection; the production rate of mature single positives matched thymic export rates and was only 3 % of double‑positive cortical production.

Abstract

We have reexamined the balance between cell birth, cell maturation, and cell death in the thymus by labeling dividing thymocytes and their progeny in vivo with [3H]-thymidine, isolating clearly defined subpopulations by fluorescence-activated cell sorting, and determining the distribution of label by autoradiography. When mature thymocytes were precisely defined (as CD4+CD8- CD3+ or CD4-CD8+ CD3+) and separated from immature single positives (CD4+CD8- CD3- and CD4-CD8+ CD3-), a lag was observed in the rate of entry of [3H]thymidine into mature cells. Thus, many of the mature thymocytes appear to derive from a small nondividing cortical thymocyte pool, rather than originating directly from the earliest dividing CD4+CD8+ blasts. There was little evidence for cell division during or after mature thymocyte formation, suggesting a one-for-one differentiation from cortical cells rather than selective clonal expansion. The rate of production of mature single positive thymocytes agreed closely with estimates of the rate of export of mature T cells from the thymus and was only 3% of the rate of production of double-positive cortical thymocytes. This was compatible with a stringent selection process and extensive intrathymic cell death and suggested that no extensive negative selection occurred after the mature cells were formed.