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Publications (10 of 66) Show all publications
Brandt, L., Pfefferle, A., Goodridge, J., Malmberg, K.-J. & Önfelt, B. (2017). Cytotoxicity and killing kinetics of KIR educated NK cells. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 301-301.
Open this publication in new window or tab >>Cytotoxicity and killing kinetics of KIR educated NK cells
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, 301-301 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-215793 (URN)000411865200127 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20171018

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Fogelqvist, E., Kördel, M., Carannante, V., Önfelt, B. & Hertz, H. (2017). Laboratory cryo x-ray microscopy for 3D cell imaging. Scientific Reports, 7, Article ID 13433.
Open this publication in new window or tab >>Laboratory cryo x-ray microscopy for 3D cell imaging
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 13433Article in journal (Refereed) Published
Abstract [en]

Water-window x-ray microscopy allows two-and three-dimensional (2D and 3D) imaging of intact unstained cells in their cryofixed near-native state with unique contrast and high resolution. Present operational biological water-window microscopes are based at synchrotron facilities, which limits their accessibility and integration with complementary methods. Laboratory-source microscopes have had difficulty addressing relevant biological tasks with proper resolution and contrast due to long exposure times and limited up-time. Here we report on laboratory cryo x-ray microscopy with the exposure time, contrast, and reliability to allow for routine high-spatial resolution 3D imaging of intact cells and cell-cell interactions. Stabilization of the laser-plasma source combined with new optics and sample preparation provide high-resolution cell imaging, both in 2D with ten-second exposures and in 3D with twenty-minute tomography. Examples include monitoring of the distribution of carbon-dense vesicles in starving HEK293T cells and imaging the interaction between natural killer cells and target cells.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Physical Sciences
Identifiers
urn:nbn:se:kth:diva-217434 (URN)10.1038/s41598-017-13538-2 (DOI)000413188400014 ()29044158 (PubMedID)2-s2.0-85031924153 (Scopus ID)
Note

QC 20171117

Available from: 2017-11-17 Created: 2017-11-17 Last updated: 2017-11-17Bibliographically approved
Verron, Q., Guldevall, K., Brandt, L., Olofsson, P. E., Frisk, T. & Önfelt, B. (2017). Microchip screening for single cell assessment and isolation of serial killing NK cells. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 347-347.
Open this publication in new window or tab >>Microchip screening for single cell assessment and isolation of serial killing NK cells
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, 347-347 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-215798 (URN)000411865200230 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Note

QC 20171018

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Carannante, V., Olofsson, K., Van Oojen, H., Edwards, S., Brismar, H., Lundqvist, A., . . . Önfelt, B. (2017). Novel platform for studying infiltration, migration and cytotoxicity of human Natural Killer cells in solid tumors. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 315-315.
Open this publication in new window or tab >>Novel platform for studying infiltration, migration and cytotoxicity of human Natural Killer cells in solid tumors
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, 315-315 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-215794 (URN)000411865200163 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Note

QC 20171018

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Meinke, S., Brandt, L., Sandgren, P., Önfelt, B. & Hoglund, P. (2017). Platelets become NK cell targets in the presence of anti-platelet antibodies. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 257-258.
Open this publication in new window or tab >>Platelets become NK cell targets in the presence of anti-platelet antibodies
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, 257-258 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-215788 (URN)000411865200028 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Note

QC 20171018

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Guldevall, K., Brandt, L., Forslund, E., Olofsson, K., Frisk, T. W., Olofsson, P. E., . . . Önfelt, B. (2016). Microchip screening Platform for single cell assessment of NK cell cytotoxicity. Frontiers in Immunology, 7, Article ID 119.
Open this publication in new window or tab >>Microchip screening Platform for single cell assessment of NK cell cytotoxicity
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2016 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, 119Article in journal (Refereed) Published
Abstract [en]

Here, we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) cells within larger populations. Human primary NK cells were distributed across a silicon-glass microchip containing 32,400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis, the numbers of NK and live or dead target cells in each well could be assessed at different time points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (approximate to 75%) were non-cytotoxic against the leukemia cell line K562, some NK cells were able to kill several (>= 3) target cells within the 12-h long experiment. In addition, the screening approach was adapted to increase the chance to find and evaluate serial killing NK cells. Even if the cytotoxic potential varied between donors, it was evident that a small fraction of highly cytotoxic NK cells were responsible for a substantial portion of the killing. We demonstrate multiple assays where our platform can be used to enumerate and characterize cytotoxic cells, such as NK or T cells. This approach could find use in clinical applications, e.g., in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2016
Keyword
NK cells, cytotoxicity, single cell analysis, microchip, screening, microscopy, fluorescence, immune synapse
National Category
Immunology
Identifiers
urn:nbn:se:kth:diva-185604 (URN)10.3389/fimmu.2016.00119 (DOI)000373340600001 ()2-s2.0-84966702164 (Scopus ID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Childhood Cancer FoundationSwedish Cancer Society
Note

QC 20160428

Available from: 2016-04-28 Created: 2016-04-25 Last updated: 2017-11-30Bibliographically approved
Hsu, H.-T., Mace, E. M., Carisey, A. F., Viswanath, D. I., Christakou, A., Wiklund, M., . . . Orange, J. S. (2016). NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing. Journal of Cell Biology, 215(6), 875-889.
Open this publication in new window or tab >>NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing
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2016 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 215, no 6, 875-889 p.Article in journal (Refereed) Published
Abstract [en]

Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein-and integrin signal-dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge during NK cell cytotoxicity, however, remains unclear. We experimentally controlled the availability of human ligands to regulate NK cell signaling and promote granule convergence with either directed or nondirected degranulation. By the use of acoustic trap microscopy, we generated specific effector-target cell arrangements to define the impact of the two modes of degranulation. NK cells with converged granules had greater targeted and less nonspecific "bystander" killing. Additionally, NK cells in which dynein was inhibited or integrin blocked under physiological conditions demonstrated increased nondirected degranulation and bystander killing. Thus, NK cells converge lytic granules and thereby improve the efficiency of targeted killing and prevent collateral damage to neighboring healthy cells.

Place, publisher, year, edition, pages
Rockefeller University Press, 2016
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-199737 (URN)10.1083/jcb.201604136 (DOI)000390414900014 ()2-s2.0-85009183766 (Scopus ID)
Note

QC 20170123

Available from: 2017-01-23 Created: 2017-01-16 Last updated: 2017-11-29Bibliographically approved
Enqvist, M., Ask, E. H., Forslund, E., Carlsten, M., Abrahamsen, G., Béziat, V., . . . Malmberg, K.-J. -. (2015). Coordinated expression of DNAM-1 and LFA-1 in educated NK cells. Journal of Immunology, 194(9), 4518-4527.
Open this publication in new window or tab >>Coordinated expression of DNAM-1 and LFA-1 in educated NK cells
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2015 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 194, no 9, 4518-4527 p.Article in journal (Refereed) Published
Abstract [en]

The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I-specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.

Keyword
alpha interferon, CD94 antigen, cell adhesion molecule, cell adhesion molecule LFA 1, DNAX accessory molecule 1, HLA E antigen, interleukin 12, interleukin 15, interleukin 18, interleukin 2, interleukin 21, killer cell immunoglobulin like receptor, natural killer cell receptor, natural killer cell receptor NKG2A, natural killer cell receptor NKG2D, unclassified drug, antigen expression, antigen presentation, antigen presenting cell, antigen recognition, Article, cell maturation, cellular distribution, conformational transition, controlled study, cytokine production, cytokine release, cytolysis, effector cell, human, human cell, immunological memory, immunological synapse, immunoregulation, lymphocyte differentiation, natural killer cell, priority journal, protein determination, protein expression, protein function, protein localization, protein protein interaction, protein targeting, receptor intrinsic activity, signal transduction
National Category
Immunology
Identifiers
urn:nbn:se:kth:diva-167771 (URN)10.4049/jimmunol.1401972 (DOI)000353727400050 ()25825444 (PubMedID)2-s2.0-84928474098 (Scopus ID)
Funder
Swedish Research CouncilSwedish Childhood Cancer FoundationSwedish Cancer SocietyThe Karolinska Institutet's Research FoundationWenner-Gren FoundationsEU, European Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20150526

Available from: 2015-05-26 Created: 2015-05-22 Last updated: 2017-12-04Bibliographically approved
Forslund, E., Sohlberg, E., Enqvist, M., Olofsson, P. E., Malmberg, K.-J. & Önfelt, B. (2015). Microchip-Based Single-Cell Imaging Reveals That CD56(dim) CD57(-)KIR(-)NKG2A(+) NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56(dim)CD57(-)KIR(-)NKG2A(-) NK Cells. Journal of Immunology, 195(7), 3374-3381.
Open this publication in new window or tab >>Microchip-Based Single-Cell Imaging Reveals That CD56(dim) CD57(-)KIR(-)NKG2A(+) NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56(dim)CD57(-)KIR(-)NKG2A(-) NK Cells
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2015 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 195, no 7, 3374-3381 p.Article in journal (Refereed) Published
Abstract [en]

NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(+) (lacking inhibitory receptors; IR-) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A(+) NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR-NK cells. NKG2A(+) NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A(+) NK cells. Conjugates involving IR- NK cells were generally more short-lived and IR- NK cells did not become activated to the same extent as NKG2A(+) NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A(+) and IR- NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A(+) NK cells is linked to processes regulating events in the recognition phase of NK-target cell contact rather than events after cytotoxicity has been triggered.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Immunology
Identifiers
urn:nbn:se:kth:diva-175487 (URN)10.4049/jimmunol.1500171 (DOI)000361741200043 ()26320254 (PubMedID)2-s2.0-84942475118 (Scopus ID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Cancer SocietyScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20151028

Available from: 2015-10-28 Created: 2015-10-16 Last updated: 2017-12-01Bibliographically approved
Goodridge, J. P., Onfelt, B. & Malmberg, K.-J. (2015). Newtonian cell interactions shape natural killer cell education. Immunological Reviews, 267(1), 197-213.
Open this publication in new window or tab >>Newtonian cell interactions shape natural killer cell education
2015 (English)In: Immunological Reviews, ISSN 0105-2896, E-ISSN 1600-065X, Vol. 267, no 1, 197-213 p.Article, review/survey (Refereed) Published
Abstract [en]

Newton's third law of motion states that for every action on a physical object there is an equal and opposite reaction. The dynamic change in functional potential of natural killer (NK) cells during education bears many features of such classical mechanics. Cumulative physical interactions between cells, under a constant influence of homeostatic drivers of differentiation, lead to a reactive spectrum that ultimately shapes the functionality of each NK cell. Inhibitory signaling from an array of self-specific receptors appear not only to suppress self-reactivity but also aid in the persistence of effector functions over time, thereby allowing the cell to gradually build up a functional potential. Conversely, the frequent non-cytolytic interactions between normal cells in the absence of such inhibitory signaling result in continuous stimulation of the cells and attenuation of effector function. Although an innate cell, the degree to which the fate of the NK cell is predetermined versus its ability to adapt to its own environment can be revealed through a Newtonian view of NK cell education, one which is both chronological and dynamic. As such, the development of NK cell functional diversity is the product of qualitatively different physical interactions with host cells, rather than simply the sum of their signals or an imprint based on intrinsically different transcriptional programs.

Keyword
natural killer cells, major histocompatibility complex, repertoire development, cytotoxicity, differentiation, cell surface molecules
National Category
Immunology
Identifiers
urn:nbn:se:kth:diva-173423 (URN)10.1111/imr.12325 (DOI)000360082000013 ()26284479 (PubMedID)2-s2.0-84939533391 (Scopus ID)
Note

QC 20150915

Available from: 2015-09-15 Created: 2015-09-11 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5178-7593

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