1,721,101 research outputs found
Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function
No full textThe Eleventh Killer Immunoglobulin-like Receptor (KIR) Workshop was held in Camogli (Genoa, Italy) in October 2018. This congress brought together 113 participants working on KIR field. Fifty-eight studies have been presented, the majority of which included unpublished data. Thus, KIR workshop, allowing the meeting of people sharing their knowledge and experience in a friendly atmosphere, still represents a special event of fruitful discussion and exchange of novel breakthrough, results, and ideas. In this report we summarize all the scientific contributions highlighting the most recent advances in KIR field. Forty abstracts, upon presenting author permission, are available at xxxxx link. This article is protected by copyright. All rights reserved
Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells.
No full textHigh performance liquid chromatographic strategy for the analysis of exopolysaccharides extracted from pathogenic bacteria.
No full textUltrastructural and cytofluorimetric analyses of blood-derived human NK cells cultured under metastatic-calcification-like conditions
No full textNatural killer (NK) cells are innate lymphoid cells involved in the immune response against virally infected or malignant cells, playing a regulatory role in adaptive immunity in both physiological and pathological conditions. NK cells are also reported to infiltrate both atherosclerotic plaques and mineralizing aortic valve leaflets1, but whether they play a pathophysiological or compensatory role in cardiovascular calcific diseases still needs more elucidation. Here, propensity of peripheral blood human NK cells to undergo mineralization was assayed culturing cells up to 8 days with a validated pro-calcific medium simulating metastatic calcification. Cells were examined by electron microscopy, for their morphological evaluation, and multiparametric flow cytometry, for the analysis of NK cell subsets as well as major HLA class I (NKG2A, KIRs) and non-HLA class I specific (i.e. NCRs) NK receptor expression. Ultrastructurally, NK cells not exposed to the pro-calcific milieu exhibited preserved organelles. Conversely, NK cells from pro-calcific cultures showed suffering signs, but appeared free from calcification. Actually, they showed not typical features of pro-calcific degeneration, such as accumulation of membrane-derived lipid material and its layering at cell edges, as previously described for mineralizing valve interstitial cells cultured under the same pro-calcific conditions2,3. Cytofluorimetric analyses showed that treatment with the pro-calcific medium reduced NK cell counts, but without altering the ratio between cell subsets (CD56brightCD16dim/- and CD56dimCD16+) and the expression of the assayed HLA receptors, compared to NK cells cultured without the pro-calcific medium. Moreover, the pro-calcific treatment seemed to slightly upregulate the NCR NKp44, without significantly affecting the expression of the other NCRs NKp30 and NKp46. Overall, these preliminary data revealed that NK cells do not undergo mineralization as well as significant phenotypic alterations even if cultured under severe pro-calcific conditions. Further investigations are ongoing to improve knowledge on possible involvement of NK cells in calcification processes.
References:
1) Passos, L.S.A.; Lupieri, A.; Becker-Greene, D.; Aikawa E. Innate and adaptive immunity in cardiovascular calcification. Atherosclerosis 2020, 306, 59-67.
2) Bonetti, A.; Della Mora, A.; Contin, M.; Tubaro, F.; Marchini, M.; Ortolani, F. Ultrastructural and spectrophotometric study on the effects of putative triggers on aortic valve interstitial cells in in vitro models simulating metastatic calcification. Anat. Rec. 2012, 295, 1117-1127.
3) Bonetti, A.; Allegri, L.; Baldan, F.; Contin, M.; Battistella, C.; Damante, G.; Marchini, M.; Ortolani, F. Critical involvement of calcium-dependent cytosolic phospholipase A2 in aortic valve interstitial cell calcification. Int. J. Mol. Sci. 2020, 21, 6398
Comparison of different CpG oligodeoxynucleotide classes for their capability to stimulate human NK cells
No full textOligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides (CpG ODN) mimic the immunostimulatory activity of microbial DNA via Toll-like receptor (TLR)9. Previous studies indicated that human NK cells express functional TLR3 and TLR9, since their cytokine release and cytolytic function could be incremented by poly(I:C) or ODN A/B, respectively. We have now evaluated the capability of a novel class of CpG ODN, termed ODN C, to modulate the function of human NK cells in the presence of exogenous cytokines. We show that NK cells isolated from peripheral blood and cultured with ODN C, in the presence of either IL-12 or IL-8, express higher levels of CD69 as compared to those stimulated with either ODN A or ODN B. Moreover, NK cells cultured with ODN C displayed higher cytolytic activity against tumor cell lines. These effects were not confined to freshly isolated peripheral blood NK cells since polyclonal NK cell populations that had been cultured in the presence of exogenous IL-2 for several weeks also displayed higher cytolytic activity and cytokine release after culture in the presence of ODN C. Remarkably, NK cells displaying poor responses to ODN A/B were efficiently stimulated by ODN C
Extending killer Ig-like receptor function: from HLA class I recognition to sensors of microbial products
No full textUptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
Full text linkThe KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4 can induce the uptake of CCR7 by KIR2DS4+ NKG2A+ NK cell clones after interacting with CCR7+ target cells expressing HLA-Cw4 and HLA-Cw6 alleles. However this interaction is not always sufficient to override the inhibition generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also show that, different from resting NK cells, the acquisition of CCR7 in response to IL-18 cannot occur in IL2-activated NK cells because of a marked downregulation in their IL-18Rα expression. As a consequence trogocytosis represents the major mechanism by which KIR2DS4+ activated NK cells acquire the expression of this chemokine receptor
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