ABSTRACT
Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called Valpha14Jalpha18 in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, alpha-galactosylceremide (alpha-GalCer), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and interferon-gamma. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with alpha-GalCer. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.
Subject(s)
Animals , Humans , Mice , Antigen-Presenting Cells , Asthma , Autoimmune Diseases , Colitis , Communicable Diseases , Encephalomyelitis, Autoimmune, Experimental , Galactosylceramides , Interferon-gamma , Interleukin-4 , Natural Killer T-Cells , Receptors, Antigen, T-Cell , T-Lymphocytes , Thyroid Gland , Thyroiditis , VirusesABSTRACT
PURPOSE: alpha-Galactosylceramide (alpha-GalCer)-stimulated human Valpha24 natural killer T (NKT) cells exert antitumor activity against some leukemia in a CD1d dependent and TCR-mediated manner, but could not kill CD1d-negative neuroblastoma (NB) cells. There are few reports about the direct antitumor effect of highly secreted cytokines by these cells on activation. In this study, using a cell-free supernatant (SPN) collected from plate bound hCD1d/alphaGalCer tetramers-stimulated NKT cells, we examined whether they could be helpful in the immunotherapeutic treatment of NB. METHODS: Cells were cultured in IMDM. The cytokines produced by NKT cells were measured with Cytometric Bead Array (CBA) analysis. Cell viability was evaluated by calcein-AM fluorescence with digital image microscopy scanning (DIMSCAN). The percentage of specific apoptosis was calculated by flow cytometric detection of apoptosis using annexin V and 7-AAD. RESULTS: The activated NKT cells secreted high levels of IL-2, INF-gamma, TNF-alpha. The SPN was significantly cytotoxic against four out of eight tested NB cell lines, through mainly apoptosis as evidenced by annexin-V staining and inhibition with the pretreatment of pancaspase blocker. This apoptosis was significantly inhibited when anti-TNF-alpha and anti-IFN-gamma neutralizing mAbs were used separately and it was completely abolished when the two mAbs were combined. CONCLUSION: IFN-gamma and TNF-alpha produced by NKT cells could exert synergistically direct anti-tumor activity through apoptosis on some NB cell lines.