Developmental program of mouse Vα14i NKT cells

Natural killer T (NKT) cells are a distinct lymphocyte lineage that regulates immune responses. During their development in the thymus, immature uncommitted double-positive CD4+CD8+ thymocytes that rearrange the semi-invariant T-cell receptor found on mature NKT cells are positively selected by the non-classical MHC class I molecule CD1d, which is expressed at the surface of cortical thymocytes. At this stage, the positively selected cells branch off from the conventional T-cell developmental program and start to acquire activated and/or memory markers and several ‘bona fide’ NK cell attributes. Recent work has started to reveal the specific developmental requirements for this divergent pathway of differentiation. These include several signal transduction molecules, transcription factors and cytokines, including T-bet, members of the NF-κB family, Fyn and IL-15.