CD107a as a functional marker for the identification of natural killer cell activity

Alter, Galit; Malenfant, Jessica; Altfeld, Marcus

doi:10.1016/j.jim.2004.08.008

Cited by 1,233 publications

(1,157 citation statements)

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“…5,[7][8][9] In this context, it is of interest that earlier studies showed that the surface expression of NKp46 may vary in different human peripheral blood NK cells, and that the NKp46 phenotype of NK clones correlates with cytolytic activity. 22 In the present study, we compared the ex vivo phenotypic and functional characteristics of circulating and intrahepatic NKp46 Dim and NKp46 High NK cells, and demonstrate that NKp46 surface density defines, phenotypically and functionally, different human NKcell subsets. Moreover, we show the intrahepatic accumulation of NKp46 High cells and present first data suggesting a role of NKp46 High NK cells in the control of viral replication and hepatic fibrogenesis in hepatitis C.…”

mentioning

confidence: 77%

“…28 Moreover, it is important to note that previous reports not only demonstrated varying expression of NKp46 in different NK-cell clones, but also suggested that density of NKp46 expression may correlate with cytolytic activity in vitro. 22,34 Therefore, we put forward the hypothesis that the NKp46 phenotype (i.e., NKp46 Dim versus NKp46 High ) defines different NK-cell subsets and studied the function of these NK-cell subpopulations as well as the role of NKp46 in hepatitis C.…”

Section: Discussionmentioning

confidence: 99%

“…Purified NK cells were coincubated with either major histocompatibility complex-deficient K562 cells or Huh7 A2 HCV replicon cells at different effector/target (E:T) ratios in the presence of anti-CD107a to assess degranulation, as described before. 22 For NKp46-mediated redirected killing assay, sorted NK-cell subsets were cultured with IL-2 (100 U/mL). The next day, NK cells were coincubated with carboxyfluorescein succinimidyl ester (CFSE)-labeled FccR þ P815 cells loaded with unconjugated antiNKp46 (10 lg/mL; R&D Systems) for 30 minutes (E:T ratios: 1:1, 1:5, and 1:10).…”

Section: Methodsmentioning

confidence: 99%

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Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

et al. 2012

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Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by a multitude of receptors, including activating NKp46 receptor. However, reports on NKp46 in hepatitis C are controversial. Therefore, we investigated the hepatic recruitment and function of NKp46(1) NK cells, considering differential surface expression of NKp46 resulting in NKp46 High and NKp46 Dim subsets. Intra-and extrahepatic NK-cell subsets from HCV-infected patients were characterized by flow cytometry. Cytotoxic activity and interferon-gamma (IFN-c) secretion were studied using K-562, P815, and primary hepatic stellate cells as targets. Anti-HCV activity of NK-cell subsets was studied using the replicon system. Density of NKp46 surface expression clearly segregated NKp46 Dim and NKp46 High subsets, which differed significantly with respect to the coexpression of maturation markers and NK-cell receptors. More important, NKp46 High NK cells showed a higher cytolytic activity and stronger IFN-c secretion than NKp46 Dim NK cells. Accordingly, NKp46 High NK cells efficiently blocked HCV replication in vitro. Blocking experiments confirmed an important role for the NKp46 receptor. Furthermore, we found an intrahepatic accumulation of NKp46 High NK cells. Of note, high cytolytic activity of NKp46 High NK cells was also confirmed in the intrahepatic NK-cell population, and the frequency of intrahepatic NKp46 High NK cells was inversely correlated with HCV-RNA levels and fibrosis stage. Conclusions: NKp46 High expression defines a specific NK-cell subset that may be involved in both the suppression of HCV replication and HCV-associated liver damage underpinning the role of NK cells in the immunopathogenesis of HCV. (HEPATOLOGY 2012;56:1201-1213 See Editorial on Page 1197 I nfection with the hepatitis C virus (HCV) often results in chronic liver disease. Elimination of HCV infection requires the coordinated function of the innate and the adaptive immune system. Natural killer (NK) cells constitute a major component of the intrahepatic lymphocyte pool. In contrast to the peripheral blood, which contains approximately 5%-10% NK cells, intrahepatic lymphocytes comprise approximately 30% NK cells, and the percentage of intrahepatic NK cells may increase >50% in liver diseases. 1 Immunogenetic analyses indicate that NK cells may influence the outcome of acute HCV infection as well as immunopathogenesis in chronic hepatitis C (CHC). 2 Accordingly, in vitro studies suggest that NK cells are able to recognize and kill HCV-infected hepatocytes in vivo. 3 However, published data on phenotype and function of NK cells in HCV infection are controversial. [4][5][6][7][8][9][10][11][12][13]

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mentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

et al. 2012

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“…Afterward, the cells were stained with directly conjugated mAbs against CD3 and CD56 for 30 min on ice, washed, resuspended in phosphate-buffered saline, and analyzed by flow cytometry. 19 IFN-c secretion assay CD3 2 CD56 1 NK cells were sorted on a FACSAria instrument at a purity of over 90%. The sorted cells were cultured and stimulated as described above.…”

Section: Analysis Of Nk Cell Degranulationmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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Major histocompatibility complex (MHC) class I chain-related protein A (MICA), which is a ligand for human NKG2D, is expressed by a variety of epithelial tumor cells and promotes the activation of natural killer (NK), CD8 1 and cd-T cells. Although ectopic expression of MICA on tumor cells elicits anti-tumor responses, soluble MICA downregulates the activities of lymphocytes. In this study, we showed that recombinant, immobilized MICA (iMICA) molecules coated on plastic wells weakly promote peripheral NK cell activation, secretion of interferon (IFN)-c and degranulation without inducing apoptosis. In addition, iMICA synergized with IL-15 and soluble 4-1BB ligand (s4-1BBL) to expand NK cells 25-to 42-fold in a 13-day culture, whereas NK cells stimulated only with IL-15 and s4-1BBL expanded 10-to 16-fold. In contrast to NK cells expanded by IL-15 and s4-1BBL stimulation, NK cells expanded long term in the presence of iMICA exhibited increased cytotoxicity against leukemia cells. These results suggest that large numbers of NK cells with high cytotoxicity can be generated by stimulation with IL-15 and s4-1BBL in the presence of iMICA and that these cells can be used for adoptive cancer immunotherapy. Studies on the 4-1BB signaling pathway have shown that ligation of 4-1BB promotes the survival and multiplication of CD8 1 T and NK cells. 6 IL-15 is essential for the development and function of NK cells. 7 Coculture of NK cells with K562 cells ectopically coexpressing 4-1BB ligand (4-1BBL) and membrane-bound IL-15 effectively promotes the expansion of NK cells in vitro and mediates their cytotoxicity against some leukemia cells. 8,9 In addition, IL-15 upregulates the expression of NKG2D on NK and T cells, even in the presence of soluble NKG2DL. 10 IL-15 and NKG2D signals cross-regulate each other and

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“…La translocación de esta molécula permite evaluar la capacidad de fusión de los gránulos citotóxicos con la membrana celular de los linfocitos NK, lo cual descarta defectos en la degranulación de las células citotóxicas de los pacientes (33,34). Para evaluar la translocación de CD107a a la superficie celular se emplearon células mononucleares de sangre periférica en todos los pacientes y linfocitos NK purificados por selección negativa con perlas magnéticas (Invitrogen TM / Dynal, Oslo-Norway) en el paciente 14.…”

Section: Ensayo De Translocación De Cd107aunclassified

Variaciones en el número y función de los linfocitos asesinos naturales durante infecciones recurrentes o graves

et al. 2013

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Introducción. Existen pocos datos sobre los defectos que afectan el desarrollo y función de los linfocitos asesinos naturales (natural killers, NK) en pacientes con un incremento anormal en la recurrencia de infecciones. Objetivo. Realizar una evaluación sistemática de las diferentes subpoblaciones y la función de estas células en pacientes con infecciones recurrentes. Materiales y métodos. Se incluyeron 20 pacientes con infecciones graves o recurrentes y se analizaron las subpoblaciones y la respuesta citotóxica de los linfocitos NK en sangre periférica. Los resultados de los pacientes se compararon con controles sanos pareados por edad y sexo. Resultados. Los pacientes con episodios infecciosos activos presentaron anormalidades transitorias en el porcentaje o el número absoluto de linfocitos NK. Se caracterizaron, además, cinco pacientes con alteraciones persistentes en la distribución de las subpoblaciones de linfocitos NK. Estas alteraciones se debieron principalmente a la disminución de células CD56 dim CD16 bright . Se evidenciaron, también, defectos en la función de los linfocitos NK en algunos de nuestros pacientes; sin embargo, estas alteraciones fueron transitorias y se asociaron principalmente a la fase activa de la enfermedad. Conclusiones. Nuestros resultados evidencian defectos transitorios en el número y función de los linfocitos NK en pacientes con infecciones recurrentes o graves, además de alteraciones persistentes en los LNK CD56 dim CD16 bright en algunos individuos. Es necesario profundizar en los mecanismos que conllevan al desarrollo de estos defectos inmunes y estudiar cómo estas alteraciones influyen en la respuesta inmune.Palabras clave: células asesinas naturales, subgrupos linfocitarios, pruebas inmunológicas de citotoxicidad, infección. doi: http://dx.doi.org/10.7705/biomedica.v34i1.1606 Variation in NK cell number and function in individuals with recurrent or severe infectionsIntroduction: The information about defects affecting natural killer cell (NK) development and activity in patients with an abnormal increase of recurrent infections is scarce. Objective: To perform a systematic analysis of NK abnormalities in patients with recurrent infections. Materials and methods: Our study enrolled twenty patients with severe or recurrent viral infections. Natural killer cell subsets, surface receptors expression and cytotoxicity were analyzed. Results were compared with those from age-and sex-matched healthy controls. Results: Transient alterations were observed in the percentages and absolute numbers of NK cells in patients with infection active episodes. We also described five patients with stable disturbances in the distribution of NK cell subpopulations. These defects are mainly due to a decrease in the CD56 dim CD16 bright cells in peripheral blood. In addition, NK cell function abnormalities were observed in some patients, however, those were always transient and mainly associated to active disease.Conclusions: These findings demonstrate transient alterations in the percentages and ...

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CD107a as a functional marker for the identification of natural killer cell activity

Cited by 1,233 publications

References 15 publications

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Variaciones en el número y función de los linfocitos asesinos naturales durante infecciones recurrentes o graves

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