CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Abstract

SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice

“…They are activated by recognizing glycolipid antigens presented by CD1d, a member of major histocompatibility complex (MHC) class I like molecules, and rapidly secrete a mixture of large amount of T-helper type 1 (T H 1) and T H 2 cytokines, such as IFN-γ, interleukin (IL)-10 and IL-4 in shaping subsequent adaptive immune responses [10]. Thus, iNKT cells can function as a bridge between the innate and adaptive immune systems, and orchestrate tissue inflammation.…”

Invariant natural killer T cells contribute to chronic-plus-binge ethanol-mediated liver injury by promoting hepatic neutrophil infiltration

“…Strikingly, these increases were significantly blunted in both Ja18 2/2 and CD1d 2/2 mice ( Figure 5). As iNKT cells are known to release a variety of pro-inflammatory cytokines as well as chemokines that may play a role in the recruitment of neutrophils, 27,28 we further examined the expression of these mediators in iNKT cells isolated from chronic-plus-binge ethanol fed mice. As illustrated in Figure 6, real-time PCR analysis showed that IFN-c mRNA was not elevated in hepatic iNKT cells from chronic-plus-binge ethanol-fed mice; however, IL-4 showed a twofold increase 3 h post-binge in these mice.…”

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

“…1,2 The NKT cell T-cell receptor recognizes glycolipids rather than peptide antigens and their unique ability to rapidly produce Th1, Th2 and Th17 cytokines enables NKT cells to participate in a wide range of immune responses. 3,4 The important regulatory role of NKT cells is evident in the association between NKT cell defects and diseases where immune dysregulation is a factor, such as autoimmune diseases, allergies and various malignancies. [5][6][7][8][9] One prominent example is the association between myelodysplastic syndrome (MDS) and NKT cell deficiency.…”