NKT cells: from totipotency to regenerative medicine

The recent discovery that natural killer T (NKT) cell nuclei are totipotent opens a novel avenue for further understanding NKT cell function in normal and diseased states. The progeny of a cloned mouse harboring the in-frame rearranged Valpha14-Jalpha18 T cell receptor in one allele showed a significant increase in NKT cell number compared with wild-type or littermate control mice that possessed a different TCR. Importantly, NKT cells from such progeny produced both interferon-gamma and interleukin-4, a hallmark of NKT cells. In these progeny, NKT cell development appeared to be instructively, rather than permissively, determined. Using embryonic stem cells prepared via the somatic cell nuclear transfer of NKT nuclei, relatively mature NKT cells were induced under conditions permissible for T cell induction. Furthermore, these NKT cells matured autonomously upon injection into mice, resulting in an antigen-specific adjuvant effect.