The authors declare to have no competing interests JSH conceived

The authors declare to have no competing interests. JSH conceived and designed the study, collected and analysed the data and drafted the manuscript. UCN, TA and HR contributed to the data collection and critically revised the manuscript. ML obtained funding for the study, discussed experiments and critically revised the manuscript. “
“Natural killer (NK) cells are affected by infection with human cytomegalovirus (HCMV) manifested by increased expression of the HLA-E binding activating receptor NKG2C. We here show that HCMV seropositivity

was associated with a profound expansion of NKG2C+CD56dim NK cells in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. PS-341 Multi-color flow cytometry revealed that the expanded NKG2C+CD56dim NK

cells displayed a highly differentiated phenotype, expressed high amounts of granzyme B and exhibited polyfunctional responses (CD107a, IFN-γ, and TNF-α) to stimulation with antibody-coated as well as HLA-E expressing target cells but not when stimulated with IL-12/IL-18. More importantly, NKG2C+CD56dim NK cells had a clonal expression pattern of inhibitory killer cell immunoglobulin-like receptors (KIRs) specific for self-HLA class I molecules, with predominant usage of KIR2DL2/3. KIR engagement dampened NKG2C-mediated activation suggesting that such biased expression of self-specific KIRs may preserve self-tolerance and limit immune-pathology www.selleckchem.com/products/rgfp966.html during viral infection. Together, these findings shed new light on how the human NK-cell compartment adjusts to HCMV infection resulting in clonal expansion and differentiation of educated

and polyfunctional NK cells. Natural killer (NK) cells have the ability to kill targets without prior sensitization and their involvement in antiviral and antitumor immunity is well established 1, 2. Recent studies have demonstrated a high degree of functional heterogeneity in the NK-cell compartment attributable to a vast network of inhibitory or activating receptors that allow these cells to recognize target cells 3, 4. Killer cell immunoglobulin-like receptors (KIR) and CD94/NKG2 heterodimers are two major types of HLA class I binding Neratinib in vivo receptors that regulate NK cell function 5, 6. Both these receptor-families exist in activating and inhibitory forms and contribute to the functional education of human NK cells by interactions with their cognate ligands 7, whereas KIR are expressed in a stochastic manner with a variegated distribution in the NK cell population 8, 9, NKG2A is expressed on all CD56bright NK cells and disappears gradually during differentiation of CD56dim NK cells 10, 11. NKG2C and NKG2A are covalently associated with CD94 12.

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