The kinetics of immature murine thymocyte development in vivo.
The dynamics of cell generation and turnover in the young adult murine thymus has been studied by in vivo administration of [6-3H]deoxythymidine, isolation of thymocyte subpopulations by negative depletion and cell sorting procedures, and assessment of dividing cells and their products by autoradiography. The flow of label through subpopulations of CD4-CD8- thymocytes defined by the markers heat stable antigen (HSA), phagocyte glycoprotein 1 (Pgp-1), interleukin 2 receptor (p55) (IL-2R), and CD3 was determined, to check the developmental sequence deduced from intrathymic transfer and molecular approaches. In addition, the flow of label 'downstream' into the CD4+CD8+ cortical populations was followed to check if cells expressing CD8 alone were obligatory intermediates. The main findings were: (i) support for the following sequence within the CD4-CD8- group: HSA++Pgp-1+IL-2R(-)----HSA++Pgp-1-IL-2R(+)----HSA++Pgp-1-IL- 2R-; (ii) the majority of cell generation and cell turnover within the CD4-CD8- population was due to the HSA++IL-2R-Pgp-1- subpopulation; (iii) the rate of cell output from the proposed intermediate CD3-CD4-CD8+ subpopulation was equivalent to only 55% of the cell output from its proposed precursor, the most mature CD4-CD8- subpopulation, suggesting that many double negatives differentiate directly (or via CD3-CD4+CD8- intermediates) into double positives; and (iv) the CD4-CD8-HSA- (and CD3+) thymic subpopulation contained very few cycling cells and turned over extremely slowly, indicating that these slowly accumulating product cells are off the mainstream of T cell development.
Egerton
M
M
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Shortman
K
K
Scollay
R
R
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D051927:CD24 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008808:Mice, Inbred CBA; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D051927:CD24 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins