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Invariant NKT Cells (invariant + nkt_cell)
Selected AbstractsNonglycosidic Agonists of Invariant NKT Cells for Use as Vaccine AdjuvantsCHEMMEDCHEM, Issue 2 2009Gopal Reddy Dr. Abstract Based on the crystal structures of human ,-GalCer,CD1d and iNKT,,-GalCer,CD1d complexes, nonglycosidic analogues of ,-GalCer were synthesized. They activate iNKT cells resulting in dendritic cell maturation and the priming of antigen-specific T and B cells. Therefore, they are attractive adjuvants in vaccination strategies for cancer and infectious diseases. [source] Invariant natural killer T cells are natural regulators of murine spondylarthritisARTHRITIS & RHEUMATISM, Issue 4 2010Peggy Jacques Objective To investigate the role of invariant natural killer T (iNKT) cells in TNF,ARE/+ mice, an animal model of spondylarthritis (SpA) with both gut and joint inflammation. Methods The frequency and activation of iNKT cells were analyzed on mononuclear cells from the lymph nodes and livers of mice, using flow cytometry with ,-galactosylceramide/CD1d tetramers and quantitative polymerase chain reaction for the invariant V,14,J,18 rearrangement. Bone marrow,derived dendritic cells (DCs) were obtained by expansion of primary cells with granulocyte,macrophage colony-stimulating factor followed by coculture with iNKT cell hybridomas, and interleukin-2 release into the cocultures was then measured by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were determined by ELISA or cytometric bead array analyses of freshly isolated DCs and iNKT cells in mixed cocultures. TNF,ARE/+ mice were backcrossed onto J,18,/, and CD1d,/, mice, and disease onset was evaluated by clinical scoring, positron emission tomography, and histology. CD1d levels were analyzed on mononuclear cells in paired blood and synovial fluid samples from patients with SpA compared with healthy control subjects. Results In the absence of iNKT cells, symptoms of gut and joint inflammation in TNF,ARE/+mice were aggravated. Invariant NKT cells were activated during the course of the disease. This was linked to an enrichment of inflammatory DCs, characterized by high levels of CD1d, particularly at draining sites of inflammation. A similar increase in CD1d levels was observed on DCs from patients with SpA. Inflammatory DCs from TNF,ARE/+ mice stimulated iNKT cells to produce immunomodulatory cytokines, in the absence of exogenous stimulation. Prolonged, continuous exposure, but not short-term exposure, to tumor necrosis factor (TNF) was found to be responsible for the enhanced DC,NKT cell crosstalk. Conclusion This mode of iNKT cell activation represents a natural counterregulatory mechanism for the dampening of TNF-driven inflammation. [source] Development and maturation of invariant NKT cells in the presence of lysosomal engulfmentEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Tiziana Plati Abstract A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T-cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection. [source] Expression of CD1d and presence of invariant NKT cells in classical Hodgkin lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Chuanhui Xu No abstract is available for this article. [source] | ||||||||||