Dendritic cell maturation overrules H-2D-mediated natural killer T (NKT) cell inhibition: Critical role for B7 in CD1d-dependent NKT cell interferon γ production

Given the broad expression of H-2 class Ib molecules on hematopoletic cells, antigen presentation pathways among CD1d expressing cells might tightly regulate CD1d-restricted natural killer T (NKT) cells. Bone marrow-derived dendritic cells (BM-DCs) and not adherent splenocytes become capable of triggering NK1.1⁺/T cell receptor (TCR)^int hepatic NKT cell activation when (a) immature BM-DCs lack H-2D^b-/- molecules or (b) BM-DCs undergo a stress signal of activation. In such conditions, BM-DCs promote T helper type 1 predominant CD1d-restricted NKT cell stimulation. H-2 class Ia-mediated inhibition involves more the direct H-2D^b presentation than the indirect Qa-1^b pathway. Such inhibition can be overruled by B7/CD28 interactions and marginally by CD40/CD40L or interleukin 12. These data point to a unique regulatory role of DCs in NKT cell innate immune responses and suggest that H-2 class Ia and Ib pathways differentially control NKT cell recognition of DC antigens.