TGF-β affects development and differentiation of human natural killer cell subsets

Human peripheral blood NK cells may be divided into two main subsets: CD56brightCD16− and CD56dimCD16+. Since TGF-β is known to influence the development of many leukocyte lineages, its effects on NK cell differentiation either from human CD34+Lin− hematopoietic progenitor/stem cells in vitro or from peripheral blood NK cells were investigated. TGF-β represses development of NK cells from CD34+ progenitors and inhibits differentiation of CD16+ NK cells. Moreover, TGF-β also results in conversion of a minor fraction of CD56brightCD16+ cells found in peripheral blood into CD56brightCD16− cells, highlighting a possible role of the former as a developmental intermediate and of TGF-β in influencing the genesis of NK subsets found in blood.