THE KINETICS OF IMMATURE MURINE THYMOCYTE DEVELOPMENT INVIVO

The dynamics of cell generation and turnover in the young adult murine thymus has been studied by in vivo administration of [6-3H]deoxythymldlne, Isolation of thymocyte subpopulations by negative depletion and cell sorting procedures, and assessment of dividing cells and their products by autoradlography. The flow of label through subpopulations of CD4-CD8- thymocytes defined by the markers heat stable antigen (HSA), phagocyte gtycoproteln 1 (Pgp-1), Interleukin 2 receptor (p55) (IL-2R), and CD3 was determined, to check the developmental sequence deduced from Intrathymlc 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-1minus;ILα2R-; (II) the majority of cell generation and cell turnover within the CD4-CD8- population was due to the HSA+ +IL-2R-Pgp-1- subpopulatlon; (III) the rate of cell output from the proposed Intermediate CD3-CD4-CD8+ subpopulatlon was equivalent to only 55% of the cell output from its proposed precursor, the most mature CD4-CD8- subpopulatlon, suggesting that many double negatives differentiate directly (or via CD3-CD4+CD- intermediates) into double positives; and (Iv) the CD4-CD8-HSA- (and CD3+) thymlc subpopulatlon 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. © 1990 Oxford University Press.