NKT cells direct monocytes into a DC differentiation pathway

Monocytes can differentiate into mac- rophages or dendritic cells (DCs). The processes that promote their differentiation along one path- way rather than the other remain unknown. NKT cells are regulatory T cells that respond function- ally to self and foreign antigens presented by CD1d molecules. Hence, in addition to contributing to antimicrobial responses, they may carry out auto- reactively activated functions when there is no in- fectious challenge. However, the immunological consequences of NKT cell autoreactivity remain poorly understood. We show here that human NKT cells direct monocytes to differentiate into imma- ture DCs. The ability to induce monocyte differen- tiation was CD1d-dependent and appeared specific to NKT cells. Addition of exogenous antigens or costimulation from IL-2 was not required but could enhance the effect. DC differentiation was a result of NKT cell secretion of GM-CSF and IL-13, cyto- kines that were produced by the NKT cells upon autoreactive activation by monocytes. NKT cells within PBMC samples produced GM-CSF and IL-13 upon exposure to autologous monocytes di- rectly ex vivo, providing evidence that such NKT cell-autoreactive responses can occur in vivo. These results show that when NKT cells are acti- vated by autologous monocytes, they are capable of providing factors that specifically direct mono- cyte differentiation into immature DCs. Thus, au- toreactively activated NKT cells may contribute to the maintenance of the immature DC population, and microbial infection or inflammatory conditions that activate NKT cells further could stimulate them to promote an increased rate of DC differentiation. J. Leukoc. Biol. 81: 000-000; 2007.