Human thymic epithelial cells inhibit IL-15-and IL-2-driven differentiation of NK cells from the early human thymic progenitors

T/NK progenitors are present in the thymus however, the thymus predominantl y promotes T cell development. In this study, we demonstrated that human th ymic epithelial cells (TEC) inhibit NK cell development. Most ex vivo human thymocytes express CD1a, indicating that thymic progenitors are predominan tly committed to the T cell lineage. In contrast, the CD1a(-)CD3(-)CD56(+) NK population comprises only 0.2% (n = 7) of thymocytes, However, we observ ed increases in the percentage (20- to 25-fold) and absolute number (13- to 71-fold) of NK cells when thymocytes mere cultured with mixtures of either IL-2, IL-7 ,and stem cell factor or IL-15, IL-7, and stem cell factor. TEC , when present in the cultures, inhibited the increases in the percentage ( 3- to 10-fold) and absolute number (3- to 25-fold) of NK cells. Furthermore , we show that TEC- derived soluble factors inhibit generation of NK-CFU an d inhibit IL15- or IL2-driven NK cell differentiation from thymic CD34(+) t riple-negative thymocytes, The inhibitory activity was found to be associat ed with a 8,000- to 30,000 Ha fraction. Thus, our data demonstrate that TEC inhibit NIC cell development from T/NK CD34(+) triple negative progenitors via soluble factor(s), suggesting that the human thymic microenviroment no t only actively promotes T cell maturation but also controls the developmen t of non-T lineage cells such as the NK lineage.