Invariant NKT cell development: focus on NOD mice

• iNKT cells develop in the thymus and are selected by CD1d expressing thymocytes.
• The expression of different markers allowed identifying three stages of development.
• iNKT1, iNKT2 and iNKT17 cells are classified by their cytokine expression profile.
• iNKT cell subsets have a heterogeneous distribution among different murine strains.
• The subsets of iNKT cells play distinct roles during immune mediated pathologies.

Natural killer T (NKT) cells are non-conventional T lymphocytes expressing a TCRαβ and several NK cell markers. Once activated, they can rapidly secrete large amounts of cytokines such as IFN-γ and IL-4. As a result they can favor both Th1 and Th2 immune responses and play a critical role in anti-pathogenic immune responses as well as in regulation of autoimmune diseases. It has now been clearly established that iNKT cells can be subdivided into three subpopulations: iNKT1, iNKT2 and iNKT17 cells. Each of these populations is characterized by the expression of a particular transcription factor, surface markers and cytokines making them functionally distinct. Interestingly, NOD mice developing autoimmune diabetes exhibit a high frequency of iNKT17 cells, which can participate in the disease.