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

Human peripheral blood NK cells may be divided into two main subsets: CD56(bright)CD16- and CD56(dim)CD16(+). Since TGF-beta 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-beta represses development of NK cells from CD34(+) progenitors and inhibits differentiation of CD16(+) NK cells. Moreover, TGF-beta also results in conversion of a minor fraction of CD56(bright)CD16(+) cells found in peripheral blood into CD56(bright)CD16(-) cells, highlighting a possible role of the former as a developmental intermediate and of TGF-beta in influencing the genesis of NK subsets found in blood.