LIMITED DEVELOPMENT CAPACITY OF THE EARLIEST EMBRYONIC MURINE THYMUS

Previous studies have demonstrated that murine thymus separates from t he pharynx during 11.5-12 days of gestation, and that the proliferatio n of thymic cells starts at this age. We characterized embryonic day 1 2 thymus in terms of the surface phenotype of the thymus cells, the fu nction 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(+) ce lls, even when embryonic day 14 thymus cells were added. However, thym us cells on embryonic day 12 contained T cell precursors that develope d into mature T cells in co-culture with deoxyguanosine-treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine-trea ted embryonic day 14 thymus lobes expressed the surface molecules I-A and H-2D, whereas these cells in embryonic day 12 thymus lobes were ne gative for these surface molecules. Thus, our findings suggest that th e embryonic day 12 thymus lobe contains T cell precursors, but that th e undeveloped thymic stromal cells are insufficient to support full T cell development.