Regulation of HLA-DR and co-stimulatory molecule expression on natural killer T cells by granulocyte-macrophage colony-stimulating factor

A subset of mononuclear cells present in most tissues coexpresses receptors of both natural killer (NK) and T cells. Although linked to antiviral immunity, the function of these putative NKT cells is uncertain. We present evidence that human CD56⁺ DR^? NKT cells exhibit hybrid adaptive and innate immune functions. These cells spontaneously lysed tumour cell targets and upon engagement of T‐cell antigen receptors secreted the cytokines interferon‐γ and granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Conversely, GM‐CSF treatment transformed the NKT cells into dendritic cells, inducing rapid expression of HLA‐DR and the co‐stimulatory molecules CD80 and CD86. The ability to stimulate tetanus toxoid‐specific responses from naïve T cells was acquired within 3 days of activating CD56⁺ NKT cells with GM‐CSF. These results suggest a potential role for NKT cells in the initiation and control of primary immunity during the acute phase of infection.