LIMITED DEVELOPMENT CAPACITY OF THE EARLIEST EMBRYONIC MURINE THYMUS

Previous studies have demonstrated that murine thymus separates from the pharynx during 11.5-12 days of gestation, and that the proliferation of thymic cells starts at this age. We characterized embryonic day 12 thymus in terms of the surface phenotype of the thymus cells, the function of the lobe in supporting T cell development in organ culture, and the precursor activity of the thymus cells in a mixed culture with deoxyguanosine-treated lobes. The phenotype of the major populatlion of embryonic day 12 thymus cells was HSA(+), CD44(+), c-kit(+), Thy-1(-), CD25(-), CD4(-), CD8(-), TcR(-), and Sea-1(-). In organ culture of embryonic day 12 thymus lobes, most of the lobes did not develop well and failed to generate CD4(+)CD8(+), CD4(+)CD8(-), or CD4(-)CD8(+) cells, even when embryonic day 14 thymus cells were added. However, thymus cells on embryonic day 12 contained T cell precursors that developed into mature T cells in co-culture with deoxyguanosine-treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine-treated embryonic day 14 thymus lobes expressed the surface molecules I-A and H-2D, whereas these cells in embryonic day 12 thymus lobes were negative for these surface molecules. Thus, our findings suggest that the embryonic day 12 thymus lobe contains T cell precursors, but that the undeveloped thymic stromal cells are insufficient to support full T cell development.