Identification of committed NK cell progenitors in adult murine bone marrow

EE Rosmaraki, I Douagi, C Roth… - European journal of …, 2001 - Wiley Online Library
European journal of immunology, 2001Wiley Online Library
Natural killer (NK) cells play important roles in innate immunity by lysing tumor and virally
infected cells and by producing cytokines including interferon‐γ. While NK cell progenitors
have been described in the fetal thymus, NK cell generation from hematopoietic stem cells
(HSC) in the bone marrow (BM) occurs throughout life, and in athymic mice and humans.
Interleukin (IL)‐15 promotes NK development in vitro and is essential for the generation of
normal numbers of NK cells in vivo. By characterizing BM cells expressing IL‐15 receptor …
Abstract
Natural killer (NK) cells play important roles in innate immunity by lysing tumor and virally infected cells and by producing cytokines including interferon‐γ. While NK cell progenitors have been described in the fetal thymus, NK cell generation from hematopoietic stem cells (HSC) in the bone marrow (BM) occurs throughout life, and in athymic mice and humans. Interleukin (IL)‐15 promotes NK development in vitro and is essential for the generation of normal numbers of NK cells in vivo. By characterizing BM cells expressing IL‐15 receptor components, we found marked heterogeneity within the IL‐2 receptor β chain+ (CD122+) subset, which included cells uniquely committed to the NK lineage. These CD122+ NK cell precursors (NKP) are negative for markers used to identify mature NK cells, including NK1.1, DX5 and members of Ly‐49 family, and fail to demonstrate natural cytotoxicity against susceptible targetcells. In vitro culture of NKP generates mature lytic NK1.1+ cells at high frequencies, while they do not give rise to T, B, myeloid or erythroid cells under appropriate conditions. NKP lack transcripts associated with early B and T cell differentiation (pTα, λ5 and CD3ϵ), but express a group of genes (IL‐15Rα, Id2, GATA‐3 and Ets‐1) and the 2B4 marker, which may define NK cell committment. We propose that NKP represent the earliest adult BM precursor uniquely restricted to the NK cell lineage.
Wiley Online Library