Circulating HLA-DR(+) natural killer cells have potent lytic ability and weak antigen-presenting cell function.

Whether a freshly isolated immune cell can be equipped with both natural killing and antigen-presenting cell (APC) function has recently become controversial in mice. We sought to probe the existence of a candidate human cell with these properties by searching for cells in healthy subjects that co-express APC surface molecules and NK cell receptors. We have found that CD3(-)CD14(-)CD19(-) mononuclear cells of human blood, spleen, liver, and lymph nodes contain two distinct populations of cells that co-express HLA-DR (DR) and CD56. Circulating CD56(+) cells expressing high levels of DR were phenotypically and functionally similar to conventional CD56(-)dendritic cells (DC). Furthermore, we demonstrate here that a separate cohort of CD56(+) cells that express low levels of DR are NK cells that possess dual function as potent killers endowed with weak APC function.