KIR2DS1-dependent acquisition of CCR7 and migratory properties by human NK cells interacting with allogeneic HLA-C2+ DCs or T-cell blasts

Marcenaro, Emanuela; Pesce, Silvia; Sivori, Simona; Carlomagno, Simona; Moretta, Lorenzo; Moretta, Alessandro

doi:10.1182/blood-2012-09-458752

Cited by 41 publications

(42 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trogocytosis of target cell molecules can lead to enhanced or sustained intracellular signaling pathways and induce de novo functional properties in receiving cells. Through acquisition and incorporation of target cell proteins in the cell membrane, the receiving cells can obtain new opportunities for interaction with other immune cell types for which ligands or receptors were previously not expressed (26,36). Through the acquisition of HLA-G and possible other EVT membrane-associated molecules, the fraction of dNK with surface HLA-G may gain the ability to interact with other decidua-resident immune cells such as decidual T cells and macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…One study demonstrated that KIR2DS1 facilitated trogocytosis of HLA-C2 molecules and associated membrane fragments from antigen presenting cells (APC) by pNK (26). A protective effect of the KIR2DS1 gene in the development of pregnancy complications was demonstrated (27).…”

Section: Kir2dl4-and Kir2ds1-expressing Dnk Have Increased Levels Ofmentioning

confidence: 99%

“…KIR2DS1-HLA-C2 interaction also facilitated uptake of plasma membrane fragments and molecules beyond the specific receptor-ligand pair. Furthermore, with the acquisition of CCR7, the pNK acquired migratory properties in response to lymph node chemokines specific for CCR7 (26). Besides its role in trogocytosis, KIR2DS1 is particularly interesting in the context of dNK and EVT interactions, because mothers who have the KIR2DS1 gene in their genome are protected to some Significance Decidual natural killer cells (dNK), the largest population of leukocytes at the maternal-fetal interface, have low cytotoxicity.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

Tilburgs

Evans

Crespo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

155

View full text Add to dashboard Cite

The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal–fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G–negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Kir2dl4-and Kir2ds1-expressing Dnk Have Increased Levels Ofmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

Tilburgs

Evans

Crespo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

155

View full text Add to dashboard Cite

show abstract

“…7,8 KIR2DL2 and KIR2DL3 recognize HLA molecules in the HLA-C1 group, whereas KIR2DL1 and the activating KIR2DS1 receptors recognize the HLA-C2 group. 9,10 To become functional, NK cells must undergo a continuous process of "education" or "licensing." [11][12][13] This phenomenon is achieved when inhibitory KIRs interact with their cognate ligand (eg, KIR2DL2 with an HLA-C molecule in the C1 group) during development.…”

Section: Introductionmentioning

confidence: 99%

Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation

Sekine

Marín

Cao

et al. 2016

Blood

View full text Add to dashboard Cite

Key Points• Patients homozygous for HLA-C2 group alleles have worse outcomes after CBT.• CB selection based on the combination of NK licensing and activating KIRs may improve outcomes after CBT.The ability of cord blood transplantation (CBT) to prevent relapse depends partly on donor natural killer (NK) cell alloreactivity. NK effector function depends on specific killer-cell immunoglobulin-like receptors (KIR) and HLA interactions. Thus, it is important to identify optimal combinations of KIR-HLA genotypes in donors and recipients that could improve CBT outcome. We studied clinical data, KIR and HLA genotypes, and NK-cell reconstitution in CBT patients (n 5 110). Results were validated in an independent cohort (n 5 94). HLA-KIR genotyping of recipient germline and transplanted cord blood (CB) grafts predicted for large differences in outcome. Patients homozygous for HLA-C2 group alleles had higher 1-year relapse rate and worse survival after CBT than did HLA-C1/C1 or HLA-C1/C2 (HLA-C1/x) patients: 67.8% vs 26.0% and 15.0% vs 52.9%, respectively. This inferior outcome was associated with delayed posttransplant recovery of NK cells expressing the HLA-C2-specific KIR2DL1/S1 receptors. HLA-C1/x patients receiving a CB graft with the combined HLA-C1-KIR2DL2/L3/S2 genotype had lower 1-year relapse rate (6.7% vs 40.1%) and superior survival (74.2% vs 41.3%) compared with recipients of grafts lacking KIR2DS2 or HLA-C1. HLA-C2/C2 patients had lower relapse rate (44.7% vs 93.4%) and better survival (30.1% vs 0%) if they received a graft with the combined HLA-C2-KIR2DL1/S1 genotype. Relapsed/ refractory disease at CBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, we propose the inclusion of KIR genotyping in graft selection criteria for CBT. HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/ S2 CB graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft. (Blood. 2016;128(2):297-312)

show abstract

“…27,28 Among the non-HLA-specific triggering receptors, NKp46, NKp30, NKp44 (collectively termed natural cytotoxicity receptors [NCRs]), 22 NKG2D, 29 DNAX accessory molecule-1 (DNAM-1; CD226), 26 and CD16 play a major role in NK cell activation. In addition, human NK cells can express HLA class I-specific activating receptors, including KIR2DS1, 30,31 KIR2DS4,32,33 and CD94/NKG2C. 26 Two main NK cell subsets characterized by distinct phenotypic and functional properties have been described, namely the CD56 bright CD16 2/low and CD56 dim CD16 1 subsets.…”

mentioning

confidence: 99%

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Pesce

Greppi

Tabellini

et al. 2017

Journal of Allergy and Clinical Immunology

Self Cite

389

386

View full text Add to dashboard Cite

Background: Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells. Objective: We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features. Methods: We performed multiparametric cytofluorimetric analysis of PD-1 1 NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays. Results: We provide unequivocal evidence that PD-1 is highly expressed (PD-1 bright ) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56 dim but not CD56 bright NK cells and is confined to fully mature NK cells characterized by the NKG2A 2 KIR 1 CD57 1 phenotype. Proportions of PD-1 bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their

show abstract

KIR2DS1-dependent acquisition of CCR7 and migratory properties by human NK cells interacting with allogeneic HLA-C2+ DCs or T-cell blasts

Cited by 41 publications

References 25 publications

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Contact Info

Product

Resources

About