Reconstitution Properties of Thymus Stem Cells in Murine Fetal Liver

Injection of day-12 murine fetal liver cells into thymus lobes of Thy-1 congenic adult recipients results in a wave of thymocyte development. The kinetics of repopulation by donor cells reaches a peak after 20-25 days. The frequency of thymic stem cells (TSC) in day-12 fetal liver was estimated, by limit dilution, as 1 in 4 x 10(4) cells. Within 8 hr of injection into a thymus lobe, fetal liver TSC commit to T-cell development, losing stem-cell activity. When fetal liver cells are maintained in culture for 7 days, with no exogenous cytokines added, and then injected intra-thymically (I.T.), thymus recolonization is not observed. However, TSC can be maintained in culture for 7 days with IL-1 beta, IL-3, IL-6, or LIF added, alone or in combination, with steel factor (SLF). Poisson analysis of fetal liver cells cultured with SLF and IL-3 together revealed a precursor frequency of 1 in 1.8 x 10(5) cells. In contrast, the frequency of TSC in adult bone marrow was estimated by limit dilution as 1 in 12,000 cells.