THE DEVELOPMENT OF T-CELL AND NON-T-CELL LINEAGES FROM CD34(+) HUMAN THYMIC PRECURSORS CAN BE TRACED BY THE DIFFERENTIAL EXPRESSION OF CD44

In addition to T-lineage cells, a small proportion of hematopoietic non-T cells are present in the human postnatal thymus. However, the origin of this minor non-T cell thymic compartment is presently unknown. In this study we have analyzed the developmental potential of the earliest human intrathymic precursors, characterized as CD34(+) cells expressing intermediate levels of CD44. We show that these CD34(+)CD44(int) thymocytes cultured with interleukin 7 were able to develop simultaneously into both T- and non-T (monocytes and dendritic cells) -lineage cells. Both developmental pathways progress through a CD1(+)CD4(+) intermediate stage, currently believed to be the immediate precursor of double positive thymocytes. However, separate progenitors for either T or non-T cells could be characterized within CD1(+)CD4(+) thymocytes by their opposite expression of CD44. Downregulated levels of CD44 identified CD1(+)CD4(+) T-lineage precursors, whereas CD44 upregulation occurred on CD1(+)CD4(+) intermediates that later differentiated into non-T cells. Therefore, commitment of human early intrathymic precursors to either T or non-T cell lineages can be traced by the differential expression of the CD44 receptor.