DIFFERENTIAL-EFFECTS OF FLK-2 FLT-3 LIGAND AND STEM-CELL FACTOR ON MURINE THYMIC PROGENITOR CELLS/

Most primitive thymic progenitors, termed CD4(low) cells (CD25(-)CD44( +)CD117(+)), retain the ability to generate multiple lymphoid lineages . T cell lineage commitment occurs as CD4(low) cells differentiate int o pro-T cells (CD24(+)CD44(+)CD117(+)). We previously reported that th e in vitro cytokine responses of CD4(low) and pro-T cells differ. Whil e Flt-3 ligand (Flt-3L) has been shown to be involved in early bone ma rrow hemopoiesis, its role in thymopoiesis has not been thoroughly exa mined. Here, we report that Flt-3L has no significant effect on pro-T cells, either by in vitro proliferation or in fetal thymic organ cultu re repopulation. In contrast, CD4(low) cells cultured in vitro for 3 d ays in IL-3 + IL-6 + IL-7 + Flt-3L generated a twofold increase in cel l number 21 days after transfer into fetal thymic organ culture that i ncreased to sixfold by day 35 when compared with the corresponding CD4 (low) cells cultured in IL-3 + IL-6 + IL-7 + stem cell factor. Additio nally, the Flt-3L-cultured CD4(low) cells displayed fetal thymic organ culture repopulation kinetics that more closely approximated those se en with freshly isolated CD4(low) cells. These data suggest that Flt-3 serves as a self-renewal or proliferation/expansion signal for CD4(lo w) cells, while the effect of stem cell factor is more likely to trans duce a differentiation signal, resulting in more rapid repopulation at the expense of cell expansion.