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