Search results for "NK cells"

NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase.

2013

Abstract Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, we show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15–mediated PI3K signalin…

Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion.

2013

Control of human cytomegalovirus (HCMV) depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1), that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region …

Identifying SARS‐CoV‐2 ‘memory’ NK cells from COVID‐19 convalescent donors for adoptive cell therapy

2021

Abstract COVID‐19 disease is the manifestation of syndrome coronavirus 2 (SARS‐CoV‐2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus‐infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID‐19 and the main characteristic of SARS‐CoV‐2‐specific‐like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS‐CoV‐2 convalescent donors indicates the presence of ‘memory’/activated NK cells as it ha…

Typing of KIR genes in unrelated hematopoietic stem cell transplants: influence of the donor KIR genotype on the outcome of the transplant.

In recent years, the anti-leukemic potential of Natural Killer (NK) cells and their role in hematologic malignancies and in Hematopoietic Stem Cell Transplants (HSCT) has attracted greater interest and a recent study by Cooley S. et al. showed a better clinical outcome when patients with Acute Myeloid Leukemia received a transplant from unrelated Group B KIR haplotypes donors. As a consequence of these results, an algorithm called "KIR B-content score" was formulated, based on the number of centromeric and telomeric Group B KIR haplotypes gene-content motifs. The KIR B-content score defines three categories of donors: Neutral donors have none or one KIR B motifs, Better donors have two or m…

Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2

2019

International audience; Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan, leading to profound changes in glycocalyx length and stiffness, as revealed by atomic force microscopy. This TRF2-dependent regulation facilitated the recruitment of MDSCs, their …

The NK Cell Response to Mouse Cytomegalovirus Infection Affects the Level and Kinetics of the Early CD8+ T-Cell Response

2012

ABSTRACT Natural killer (NK) cells and CD8 + T cells play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in modulating the CD8 + T-cell response to MCMV infection is still the subject of intensive research. For analyzing the impact of NK cells on mounting of a CD8 + T-cell response and the contribution of these cells to virus control during the first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are specifically activated through the Ly49H receptor engaged by the MCMV-encoded ligand m157. Our results indicate that the requirement for CD8 + T cells in early MCMV control inversely correlates with the engagement of Ly49H. W…

Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

2013

Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complem…

Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease

2021

Abstract In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response…

Dacarbazine mediate antimelanoma effects via NK cells.

2013

International audience; Melanoma is a highly chemoresistant and metastatic tumor that, in the absence of BRAF mutations, is generally treated with the alkylating agent dacarbazine (DTIC). We discovered that DTIC upregulates the expression of NKG2D ligands on tumor cells, leading to the activation of natural killer (NK) and CD8(+) T cells. These observations underscore the immunogenic properties of DTIC and provide a rationale to combine DTIC with immunotherapeutic agents.

Immune Modulating Effects of NKT Cells in a Physiologically Low Dose Leishmania major Infection Model after αGalCer Analog PBS57 Stimulation

2014

Leishmaniasis is a parasitic infection affecting ∼12 million people worldwide, mostly in developing countries. Treatment options are limited and no effective vaccines exist to date. Natural Killer T (NKT) cells are a conserved innate-like lymphocyte population with immunomodulating effects in various settings. A number of reports state a role of NKT cells in different models of Leishmania infection. Here, we investigated the effect of NKT cells in a physiologically relevant, intradermal low dose infection model. After inoculation of 103 infectious-stage L. major, comparable numbers of skin-immigrating NKT cells in both susceptible BALB/c mice and resistant C57BL/6 mice were noted. Compared …