g. interleukin (IL)-12, IL-18 and interferon (IFN)-α]; (iii) APC intrinsic factors such

as differentiation state (e.g. monocyte versus DC) and Toll-like receptor (TLR) stimulation. Together with recent findings that demonstrate new links between NKT cell activation and endogenous lipid metabolism, these results outline a picture in which the functions of NKT cells are closely attuned to the existing biological context. Thus, NKT cells may actively promote tolerance until a critical level of danger signals arises, Y-27632 in vivo at which point they switch to activating pro-inflammatory immune responses. Natural killer T (NKT) cells were first identified as a small population of T cells in naïve mice that

express CD161 (also called NK1.1 or NKR-P1A), a marker that is characteristic of natural killer (NK) cells.1 It subsequently became clear that most of these T cells are restricted by CD1d, a non-classical type of antigen-presenting molecule with structural similarity to major histocompatibility complex (MHC) class I proteins.2,3 Further studies have revealed that, while NKT cells often express NK receptors, these are not specific lineage markers for CD1d-restricted T cells.4,5 Moreover, while NKT cells share some functional and gene expression patterns with NK cells and cytotoxic T lymphocytes (CTLs), they also have many prominent features that are more frequently associated with helper T cells.6–8 Thus, RO4929097 cost while NKT cells are an innate

T lymphocyte population, the implication from their name that they function predominantly as cytolytic effectors is not entirely accurate. Instead, a number of observations suggest that a major role of NKT cells is to serve as a type of regulatory T cell that can drive downstream immune responses along either pro-inflammatory or silencing pathways. Support for this view comes from findings that NKT cells produce a wide variety of cytokines, including both T helper type 1 (Th1) and Th2 types; that mice genetically deficient in NKT cells show defects not only in resistance to microbial Aldol condensation infections and in tumour immunosurveillance but also in establishing peripheral tolerance and preventing autoimmunity; and that specific activation of NKT cells in vivo can inhibit the onset of autoimmune diseases as well as promote microbial clearance or tumour rejection.9–11 This evidence suggests that, despite their small population size, NKT cells have potent effects on immune responses, and they facilitate different outcomes in different contexts. These properties are probably in large part a result of the ability of NKT cells to influence the functions of critical antigen-presenting cell (APC) types.