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Formation of the adaptive-like NK cell subset in response to HCMV infection is associated with epigenetic rearrangements, accompanied by multiple changes in the protein expression. This includes a decrease in the expression level of the adapter chain FcεRIγ, NKp30, and NKG2A receptors and an increase in the expression of NKG2C receptor, some KIR family receptors, and co-stimulating molecule CD2. Besides, adaptive-like NK cells are characterized by surface expression of CD57, a marker of highly differentiated cells. Here, it is shown that CD57-negative CD56 NKG2C NK cells may undergo the same changes, as established by the similarity of the phenotypic expression pattern with that of the adaptive-like CD57 NKG2C NK cells. Regardless of their differentiation stage, NKG2C-positive NK cells had increased HLA-DR expression indicating an activated state, both ex vivo and after cultivation in stimulating conditions. Additionally, CD57 NKG2C NK cells exhibited better proliferative activity compared to CD57 NKG2C and NKG2C NK cells, while retaining high level of natural cytotoxicity. Thus, CD57 NKG2C NK cells may represent a less differentiated, but readily expanding stage of the adaptive-like CD57 NKG2C NK cells. Moreover, it is shown that NK cells have certain phenotypic plasticity and may both lose NKG2C expression and acquire it de novo during proliferation, induced by IL-2 and K562-mbIL21 feeder cells.
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http://dx.doi.org/10.1002/JLB.1MA0720-654RR | DOI Listing |
Front Immunol
November 2024
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Background: Human memory NK cells represent a heterogeneous CD56 population that expands and persists in human cytomegalovirus (HCMV)-seropositive healthy individuals. They are characterized by the preferential, not fully overlapping, expression of NKG2C (activating receptor for HLA-E) and CD57 maturation marker, and by the lack of FcεRIγ adaptor chain. Hyperresponsiveness to Fcγ receptor IIIA (CD16) engagement represents the distinctive functional signature of memory NK cells.
View Article and Find Full Text PDFFront Immunol
November 2024
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
Cytotoxic activity is a hallmark of the immunopathogenesis in human cutaneous leishmaniasis (CL). In this study, we identified accumulation of CD4 granzyme B producing T cells with increased cytotoxic capacity in CL lesions. These cells showed enhanced expression of activating NK receptors (NKG2D and NKG2C), diminished expression of inhibitory NKG2A, along with the upregulation of the senescence marker CD57.
View Article and Find Full Text PDFJCI Insight
September 2024
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells.
View Article and Find Full Text PDFSci Rep
June 2024
Department of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council (CNB-CSIC), Darwin, 3, 28049, Madrid, Spain.
The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56CD16), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2024
Primate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, Germany.
HLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression.
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