Multiple hats for natural killers

Natural killer (NK) cells are a subset of lymphocytes that kill virus-infected or cancerous cells and influence adaptive immune responses via production of inflammatory cytokines. Unlike B and T lymphocytes, no transcription factors have been identified that are essential for the emergence of NK cell progenitors from their multipotent precursors. We argue that this dearth of essential factors is because of the expression of redundant transcription factors that function at the earliest stages of development. However, multiple essential transcription factors have been identified at later stages of development. Recent studies have revealed novel subsets of NK cells with differing potential for target cell lysis and cytokine production. How these subsets arise from the conventional pathway of NK cell development and identification of the transcriptional networks that control their development are major challenges for future studies.