The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions

Invariant natural killer T cells (iNKT cells) have an innate immunity-like rapidity of response and the ability to modulate the effector functions of other cells. We show here that iNKT cells specifically expressed the BTB-zinc finger transcriptional regulator PLZF. In the absence of PLZF, iNKT cells developed, but they lacked many features of innate T cells. PLZF-deficient iNKT cells accumulated in lymph nodes rather than in the liver, did not express NK markers and did not have the characteristic activated phenotype. PLZF-deficient iNKT cells failed to secrete large amounts of interleukin 4 and interferon-γ after activation; however, some cells produced either interleukin 4 or interferon-γ but not both. PLZF, therefore, is an iNKT cell-specific transcription factor that is necessary for full functionality.