NKT cells comprise a small T cell subset that appears to have far-reaching and remarkably varied effects on immune function. The mechanisms by which NKT cells affect down-stream immune responses remain poorly understood. In our preliminary studies we have observed that human NKT cells direct fresh peripheral blood monocytes to differentiate into dendritic cells (DCs) in vitro. The resulting DCs have a unique regulatory phenotype, and appear to silence MHC-restricted T cell activation. Hence, we hypothesize that promoting the differentiation of regulatory DCs is one mechanism by which NKT cells can broadly affect immune responses. However, it remains unclear whether NKT cells can perform this function in vivo. Here we propose i) to test the ability of human NKT cells to direct human monocyte differentiation into DCs after transfer into SCID-mouse hosts, and ii) to investigate the functional properties of NKT cell-induced human DCs within the SCID mice. Abstract Narrative: This grant proposes to use an in vivo SCID mouse system to investigate the functions of human NKT cells in promoting monocytes to differentiate into DCs, and to test the functional properties of the resulting DCs.
