The role of chemokine receptors in CD1D-restricted NK T cell trafficking

CD1d-restricted NK T cells influence the outcome of diverse immune responses, ranging from autoimmune conditions to host defense against pathogens and are believed to exert their effects through the rapid production of high levels of cytokines, including IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-13. Although CD1d-restricted NK T cells exhibit activity in various immune models, the trafficking patterns of these cells are not well understood.; In these studies, we characterized the chemokine receptor expression profile of human CD1d-restricted NK T cells and determined that these cells express a chemokine receptor profile indicative of Th1-inflammatory homing cells. Based on this data, we generated hypotheses about the homeostatic and inflammatory trafficking patterns of murine CD1d-restricted NK T cells. We further hypothesized that the expression of the inflammatory homing chemokine receptors, CXCR3 and CCR5 are critical for homeostatic trafficking and baseline tissue localization of CD1d-restricted NK T cells in vivo and play a significant role in recruitment of CD1d-restricted NK T cells to sites of inflammation following Th1- or Th2-mediated immune challenge.; These studies suggest that CD1d-restricted NK T cells are likely to act in the tissue rather than secondary lymphoid organs. Surprisingly, although conventional memory T cells recirculate and establish homeostasis in vivo, CD1d-restricted NK T cells remain predominantly tissue resident. However, CD1d-restricted NK T cells traffic following Th1- and Th2-mediated immune challenge. In addition, the absence of CXCR3 and/or CCR5 altered CD1d-restricted NK T cell trafficking in a Th1-mediated model of inflammation. These data suggest a central role for CD1d-restricted NK T cells in immune surveillance of tissue sites and provide a mechanism for their recruitment to inflammatory sites following immune challenge.