Skip to main content
. 2010 Aug;130(4):471–483. doi: 10.1111/j.1365-2567.2010.03293.x

Figure 1.

Figure 1

Interactions between invariant natural killer T (iNKT) cells and myeloid antigen-presenting cells (APCs) that produce pro-inflammatory outcomes. (a) Activation of iNKT cells by the strong agonist α-galactosylceramide (α-GalCer). Presentation of α-GalCer by CD1d molecules on immature dendritic cells (DCs) induces robust iNKT cell activation that is associated with both calcium and mitogen-activated protein (MAP) kinase signalling, and results in their secretion of interferon (IFN)-γ and in strong up-regulation of cell surface CD40L. These signals induce maturation of the DCs into an inflammatory phenotype that shows sustained production of interleukin (IL)-12p70 and increased expression of costimulatory molecules such as CD86, as well as the cytotoxic T lymphocyte (CTL)-licensing molecule CD70. Naïve T cells that interact with these DCs are efficiently stimulated to proliferate, and CD4+ T cells acquire a T helper type 1 (Th1) phenotype, while CD8+ T cells are licensed to become efficient killers. References: 44,64–68. (b) The indirect pathway of natural killer T (NKT) cell activation in microbial infection. In response to Toll-like receptor (TLR)-mediated recognition of microbial compounds, immature DCs produce pro-inflammatory cytokines such as IL-12 and IL-18. Although the NKT cells that interact with these DCs may receive only relatively weak T-cell receptor (TCR) stimulation from self antigen recognition, costimulation by the DC cytokines activates them to secrete IFN-γ. The effect of this interaction on DC maturation is not known. However, it is possible that the combination of a microbial TLR stimulus along with CD40L and IFN-γ from NKT cells might induce the DCs to mature into a pro-inflammatory phenotype that could further participate in downstream immune responses. References: 41,44–46. (c) Conversion of myeloid-derived suppressor cells (MDSCs) into pro-inflammatory APCs. NKT cells that are activated by recognition of either α-GalCer or self antigen on immune-suppressive MDSCs up-regulate their cell surface CD40L. In conjunction with other inflammatory signals (e.g. from pathogens or possibly tumours), the resulting CD40 stimulation of the MDSCs converts them into pro-inflammatory APCs that no longer produce the immunosuppressive enzymes arginase 1 and nitric oxide synthase 2 (NOS2) and have increased expression of costimulatory molecules such as CD86. References: 59,77.