--[@B58]). In addition, both IL-12 and IL-18 proinflammatory cytokines induced following bacterial infection that suppresses type I NKT cell motility in liver sinusoids of Cxcr6gfp/+ mice via a CD1d-independent mechanism. This block in NKT cell movement is evident within 1 h after exposure to the cytokines and precedes NKT cell activation. Further antigen ligation stabilizes an immune synapse formed between NKT cells and interacting APCs. This synapse potentiates LFA-1/ICAM-1 interactions that enable activated type I NKT cells to remain in the liver. Thus, activated type I NKT cells recirculate less than activated conventional CD4^+^ T cells ([@B59]). Identification of the patterns and kinetics of recirculation of type I and type II mouse NKT cells as well as the patterns and kinetics of human type I and type II NKT cells await further study.

Future Challenges {#S6}
=================

A future goal of studies of human NKT cells is to identify their functional roles in health and disease ([@B1]). Determination of how subsets of human NKT cells migrate and recirculate *in vivo* may advance our understanding of the biology and mechanisms of cellular interaction of different human NKT cells with APCs. Current investigations are being performed in two animal models. First, Cxcr6gfp/+ mice are being used to monitor human NKT cell trafficking, localization, and activation *in vivo* ([@B56]). Second, the kinetics and dynamics of human CD1d (hCD1d)-restricted NKT cell interactions are being analyzed in hCD1d knock-in mice that express hCD1d in place of mCD1d ([@B59]). Subpopulations of mouse type I NKT cells that are similar to human type I NKT cells in phenotype (mouse Vβ8^+^, human Vβ11 homolog^+^, CD4^low^), tissue distribution, and function (anti-tumor activity) are present in hCD1d knock-in mice. The latter mice serve to model how a lipid antigen induces the migration and function of hCD1d-restricted type I NKT cells and type II NKT cells *in vivo* ([@B59]--[@B62]). If type I and type II human NKT cells can be d