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NKT cells expressing the invariant Vα14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant Vα14 receptor with anti‐CD3 or a ligand, α‐galactosylceramide (α‐GalCer), triggers activation of Vα14 NKT cells, resulting in a rapid cytokine production such as IFN‐γ and IL‐4. Soon after their receptor activation, Vα14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with α‐GalCer (α‐GalCer/CD1d tetramer), which has been believed to be due to apoptotic cell death. Here we show that such a disappearance was largely attributed to down‐regulation of the Vα14 receptor. In fact, Vα14 NKT cells were relatively resistant to apoptosis compared to the conventional T cells as evidenced by less staining with Annexin‐V, a limited DNA fragmentation, and their preferential expression of anti‐apoptotic genes such as NAIP and …