Harnessing NKT cells for vaccination

Natural killer T (NKT) cells are innate-like T cells capable of enhancing both innate and adaptive immune responses. When NKT cells are stimulated in close temporal association with co-administered antigens, strong antigen-specific immune responses can be induced, prompting the study of NKT cell agonists as novel immune adjuvants. This activity has been attributed to the capacity of activated NKT cells to act as universal helper cells, with the ability to provide molecular signals to dendritic cells and B cells that facilitate T cell and antibody responses, respectively. These signals can override the requirement for conventional CD4⁺ T cell help, so that vaccines can be designed without need to consider CD4⁺ T cell repertoire and major histocompatibility complex Class II diversity. Animal studies have highlighted some drawbacks of the approach, namely, concerns around induction of NKT cell hyporesponsiveness, which may limit vaccine boosting, and potential for toxicity. Here we highlight studies that suggest these obstacles can be overcome by targeted delivery in vivo. We also feature new studies that suggest activating NKT cells can help encourage differentiation of T cells into tissue-resident memory cells that play an important role in prophylaxis against infection, and may be required in cancer therapy.