IMMUNOBIOLOGY

The CD4 coreceptor is crucial in the acti-vation of major histocompatibility com-plex (MHC) class II restricted CD4 T lymphocytes by binding the same MHC class as the T-cell receptor (TCR) and by potentiating TCR-dependent signaling. CD4 is also expressed by invariant natu-ral killer T cells (iNKT), which recognize natural and synthetic lipid antigens, such as -galactosyl ceramide (-GalCer), in association with the MHC class I–like CD1d molecule. Human iNKT cells can be divided into 2 major subsets depending on CD4 expression: CD4 iNKT preferen-tially produce T-helper (Th)0/Th2 cyto-kines, whereas CD4 iNKT cells produce Th1 cytokines after antigenic activation. Cytokines produced by iNKT may have immunomodulatory roles in various phys-iopathologic contexts, but their mode of regulation by iNKT cells remains ill-defined. Using blocking reagents neutral-izing CD4 binding, experimental systems where MHC class II molecules are absent and recombinant -GalCer/CD1d com-plexes, we show that CD4 potentiates human iNKT cell activation by engaging CD1d molecules. These results indicate that the CD4 coreceptors may contribute to the fine tuning of iNKT cells reactivity