Human thymic stroma supports human natural killer (NK) cell development from immature progenitors

NK cells are lymphocytes which exhibit spontaneous cytotoxicity against a variety of target cells, including cancer cells. Mature NK and T cells may derive from a common precursor which differentiates into T or NK cells depending on the microenvironment. We evaluated the effect of human fetal thymic stroma on human CD34+Lin- progenitors. The culture medium was supplemented with human AB serum with or without interleukin-2 (IL2; 1000 U/ml) and interleukin-7 (IL7; 1000 U/ml). After 3 weeks of culture, CD45/56 cells were detected by flow cytometry and their activity was tested against K562 targets. In cultures with IL2 the percentage of CD56-positive cells was much higher in the Transwell cultures (60.8 +/- 12.5% from CD34+Lin-DR+ and 51% from CD34+Lin-progenitors) than in adherent cultures (25 +/- 21.9% from CD34+Lin-DR+ and 25.3 +/- 9.5% from CD34+Lin-progenitors) or suspension cultures (23 +/- 21.4% from CD34+Lin-DR+ progenitors and 43.1 +/- 14.2% from CD34+Lin-progenitors). Cytolytic activity as measured by K562 lysis was also higher in Transwell cultures with IL2. NK cells were also obtained in cultures without factors or supplemented with IL7, but in smaller numbers. These data indicate that NK cells can be obtained in vitro by coculture of immature hematopoietic progenitors with thymic stromal cells and that IL2 appears to strongly favor their development in the absence of stromal contact. This would indicate a direct inhibitory effect of the thymic stroma on NK progenitors.