Multiple evolutionarily conserved T cell populations with innate characteristics are present in mice and humans that differ in their antigen receptor expression and their functional properties [1,2]. In mice, invariant Natural Killer T cells (iNKT), which express an invariant Va14-Ja18 T cell receptor alpha (TCRa) chain that can pair with a limited number of TCRb chains (Vb2, Vb7 and Vb8.1–۸٫۲), are the most abundant innate T cell population. These cells recognize glycolipid antigens presented by the non-classical, non-polymorphic Major Histocompatibility Complex (MHC) I family molecule CD1D. The majority of iNKT cells follow the same developmental trajectories in the thymus as conventional T cells; however, iNKT cells mature in the thymus and acquire a phenotype reminiscent of antigen-experienced T cells during development. The frequency and number of iNKT effector subsets varies between naı¨ve mouse strains and human individuals and influences the fate of bystander immune cells, even at the steady state [3–۵]. Due to their poised state, iNKT cells produce a vast amount of a variety of cytokines rapidly after activation, thereby influencing the functions of a number of innate and adaptive immune cells. iNKT cells have been implicated as positive or negative regulators of a wide range of diseased states, including microbial infection, cancer and autoimmunity and they are being targeted in immune therapies and vaccination strategies [6,7].