CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset
Open accessAbstract
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57 is a marker of terminal differentiation on human CD8+ T cells. Very few newborn or fetal NK cells express CD57; however, the frequency of CD57-bearing NK cells increases with age. We assessed the transcriptional, phenotypic, and functional differences between CD57+ and CD57− NK cells within the CD56dim mature NK subset. CD57+ NK cells express a repertoire of NK-cell receptors, suggestive of a more mature phenotype, and proliferate less when stimulated with target cells and/or cytokines. By contrast, a higher frequency of CD57+ NK cells produced interferon-γ and demonstrated more potent lytic activity when these cells were stimulated through the activating receptor CD16; however, they are less responsive to stimulation by interleukin-12 and interleukin-18. Finally, CD57 expression is induced on CD57−CD56dim NK cells after activation by interleukin-2. A combination of a mature phenotype, a higher cytotoxic capacity, a higher sensitivity to stimulation via CD16, with a decreased responsiveness to cytokines, and a decreased capacity to proliferate suggest that CD57+ NK cells are highly mature and might be terminally differentiated.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CD57+CD3- NK cells are terminally differentiated, have higher cytolytic capabilities, act as innate immune regulators, are less responsive to cytokines, and are connected to autoimmunity and immunodeficiency.
“These NK cells are functionally different than traditional, CD56 + NK cells-they are terminally differentiated and have higher cytolytic capabilities, and generally act as innate immune regulators despite being less responsive to cytokines and connected to autoimmunity and immunodeficiency (Lopez-Verges et al, 2010;Nielsen et al, 2013).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Lopez-Verges et al, 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104702 · Cited by 3,067 · see citing works
Caligiuri, M. A. (2008) · Blood · doi:10.1182/blood-2007-09-077438 · Cited by 1,910 · see citing works
Adaptive Immune Features of Natural Killer Cells
Sun, J. C., Beilke, J., & Lanier, L. (2009) · Nature · doi:10.1038/nature07665 · Cited by 1,647 · see citing works
Self-citationHuman natural killer cells: a unique innate immunoregulatory role for the CD56bright subset
Cooper, M. A., Fehniger, T. A., Turner, S. C., Chen, K. S.-M., Ghaheri, B. A., Ghayur, T., Carson, W. E., & Caligiuri, M. A. (2001) · Blood · doi:10.1182/blood.v97.10.3146 · Cited by 1,448 · see citing works
Licensing of natural killer cells by host major histocompatibility complex class I molecules
Kim, S., Poursine‐Laurent, J., Truscott, S. M., Lybarger, L. P., Song, Y.-J., Yang, L., French, A. R., Sunwoo, J. B., Lemieux, S., Hansen, T. H., et al. (2005) · Nature · doi:10.1038/nature03847 · Cited by 1,328 · see citing works
Human NK Cell Education by Inhibitory Receptors for MHC Class I
Anfossi, N., André, P., Guia, S., Falk, C. S., Roetynck, S., Stewart, C. A., Breso, V., Frassati, C., Reviron, D., Middleton, D., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.013 · Cited by 1,207 · see citing works
Lanier, L. L., Le, A. M., Civin, C., Loken, M. R., & Phillips, J. H. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.12.4480 · Cited by 1,130 · see citing works
Self-citationBrenchley, J. M., Karandikar, N. J., Betts, M. R., Ambrozak, D. R., Hill, B. J., Crotty, L. E., Casazza, J. P., Kuruppu, J., Migueles, S. A., Connors, M., et al. (2003) · Blood · doi:10.1182/blood-2002-07-2103 · Cited by 1,073 · see citing works
Skewed maturation of memory HIV-specific CD8 T lymphocytes
Champagne, P., Ogg, G. S., King, A. S., Knabenhans, C., Ellefsen, K., Nobile, M., Appay, V., Rizzardi, G. P., Fleury, S., Lipp, M., et al. (2001) · Nature · doi:10.1038/35065118 · Cited by 1,002 · see citing works
Bryceson, Y. T., March, M., Ljunggren, H., & Long, E. O. (2005) · Blood · doi:10.1182/blood-2005-04-1351 · Cited by 863 · see citing works
Lanier, L. L., Le, A. M., Phillips, J. H., Warner, N. L., & Babcock, G. F. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.131.4.1789 · Cited by 847 · see citing works
Self-citationBjörkström, N. K., Riese, P., Heuts, F. W. H., Andersson, S., Fauriat, C., Ivarsson, M. A., Björklund, A. T., Flodström‐Tullberg, M., Michaëlsson, J., Rottenberg, M. E., et al. (2010) · Blood · doi:10.1182/blood-2010-04-281675 · Cited by 734 · see citing works
Comparative studies of human FcRIII-positive and negative natural killer cells.
Nagler, A., Lanier, L. L., Cwirla, S. E., & Phillips, J. H. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.10.3183 · Cited by 694 · see citing works
Self-citationImai, C., Iwamoto, S., & Campana, D. (2005) · Blood · doi:10.1182/blood-2004-12-4797 · Cited by 661 · see citing works
Fehniger, T. A., Shah, M. H., Turner, M. J., VanDeusen, J. B., Whitman, S. P., Cooper, M. A., Suzuki, K., Wechser, M. A., Goodsaid, F., & Caligiuri, M. A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4511 · Cited by 651 · see citing works
Fernandez, N. C., Treiner, E., Vance, R. E., Jamieson, A. M., Lemieux, S., & Raulet, D. H. (2005) · Blood · doi:10.1182/blood-2004-08-3156 · Cited by 589 · see citing works
IL-15 trans-presentation promotes human NK cell development and differentiation in vivo
Huntington, N. D., Legrand, N., Alves, N. L., Jaron, B., Weijer, K. C., Plet, A., Corcuff, E., Mortier, E., Jacques, Y., Spits, H., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20082013 · Cited by 578 · see citing works
Romagnani, C., Juelke, K., Falco, M., Morandi, B., D’Agostino, A., Costa, R., Ratto, G. B., Forte, G., Carrega, P., Lui, G., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.4947 · Cited by 494 · see citing works
Evolutionary struggles between NK cells and viruses
Lanier, L. L. (2008) · Nature reviews. Immunology · doi:10.1038/nri2276 · Cited by 452 · see citing works
Self-citationCaligiuri, M. A., Zmuidzinas, A., Manley, T. J., et al. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.5.1509 · Cited by 442 · see citing works
Chan, A. T. Y., Hong, D., Atzberger, A., Kollnberger, S., Filer, A. D., Buckley, C. D., McMichael, A. J., Enver, T., & Bowness, P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.1.89 · Cited by 366 · see citing works
Voehringer, D., Koschella, M., & Pircher, H. (2002) · Blood · doi:10.1182/blood-2002-02-0657 · Cited by 352 · see citing works
Self-citationWhat is a natural killer cell?
Moretta, A., Bottino, C., Mingari, M. C., Biassoni, R., & Moretta, L. (2002) · Nature Immunology · doi:10.1038/ni0102-6 · Cited by 345 · see citing works
Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes.
Lanier, L. L., Ruitenberg, J. J., & Phillips, J. H. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.10.3478 · Cited by 310 · see citing works
Self-citationEducation of human natural killer cells by activating killer cell immunoglobulin-like receptors
Fauriat, C., Ivarsson, M. A., Ljunggren, H., Malmberg, K., & Michaëlsson, J. (2009) · Blood · doi:10.1182/blood-2009-09-245746 · Cited by 305 · see citing works
Tarazona, R., DelaRosa, O., Alonso, C., Ostos, B., Espejo, J., Peña, J., & Solana, R. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00199-8 · Cited by 262 · see citing works
Chattopadhyay, P. K., Betts, M. R., Price, D. A., Emma Gostick, D., Horton, H., Roederer, M., & Rosa, S. C. D. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0208107 · Cited by 260 · see citing works
CD57+ T lymphocytes and functional immune deficiency
Focosi, D., Bestagno, M., Burrone, Ó. R., & Petrini, M. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0809566 · Cited by 253 · see citing works
Cooley, S., Xiao, F., Pitt, M., Gleason, M., McCullar, V., Bergemann, T. L., McQueen, K. L., Guethlein, L. A., Parham, P., & Miller, J. S. (2007) · Blood · doi:10.1182/blood-2006-07-036228 · Cited by 225 · see citing works
Vitale, M., Chiesa, M. D., Carlomagno, S., Romagnani, C., Thiel, A., Moretta, L., & Moretta, A. (2004) · European Journal of Immunology · doi:10.1002/eji.200425100 · Cited by 194 · see citing works
Ibegbu, C., Xu, Y., Harris, W. B., Maggio, D. M., Miller, J. D., & Kourtis, A. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.6088 · Cited by 183 · see citing works
CD27 Defines Phenotypically and Functionally Different Human NK Cell Subsets
Vossen, M. T. M., Matmati, M., Hertoghs, K. M. L., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.3739 · Cited by 176 · see citing works
Bandrés, E., Merino, J., Vázquez, B., Inogés, S., Moreno, C., Subirá, M. L., & Sánchez-Ibarrola, A. (2000) · Clinical Immunology · doi:10.1006/clim.2000.4894 · Cited by 174 · see citing works
Use of the Intracellular Fluorescent Dye CFSE to Monitor Lymphocyte Migration and Proliferation
Parish, C. R., Glidden, M. H., Quah, B., et al. (2009) · Current Protocols in Immunology · doi:10.1002/0471142735.im0409s84 · Cited by 166 · see citing works
Receptor-induced death in human natural killer cells: involvement of CD16.
Ortaldo, J. R., Mason, A. T., & O’Shea, J. J. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.1.339 · Cited by 135 · see citing works
Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8+CD57+CD28− compartment
Sze, D., Giesajtis, G., Brown, R. D., Raitakari, M., Gibson, J., Ho, P. J., Baxter, A. G., Groth, B. F. D. S., Basten, A., & Joshua, D. (2001) · Blood · doi:10.1182/blood.v98.9.2817 · Cited by 133 · see citing works
Abo, T., Miller, C. A., & Balch, C. M. (1984) · European Journal of Immunology · doi:10.1002/eji.1830140707 · Cited by 132 · see citing works
KIR2DL4 (CD158d) Genotype Influences Expression and Function in NK Cells
Goodridge, J. P., Witt, C. S., Christiansen, F., & Warren, H. S. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.4.1768 · Cited by 126 · see citing works
Priol, Y. L., Puthier, D., Lécureuil, C., Combadière, C., Debré, P., Nguyen, C., & Combadière, B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.8.5145 · Cited by 125 · see citing works
Progressive decrease of CD8high+ CD28+ CD57− cells with ageing
Merino, J., Martínez‐González, M. Á., Rubio, M. F., Inogés, S., Sánchez-Ibarrola, A., & Subirá, M. L. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00551.x · Cited by 117 · see citing works
Human NK cells: from HLA class I‐specific killer Ig‐like receptors to the therapy of acute leukemias
Moretta, A., Locatelli, F., & Moretta, L. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00651.x · Cited by 114 · see citing works
Carson, W. E., Fehniger, T. A., & Caligiuri, M. A. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270203 · Cited by 110 · see citing works
Telomere Length in Human Natural Killer Cell Subsets
Ouyang, Q., Baerlocher, G. M., Vulto, I. M., & Lansdorp, P. M. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1392.001 · Cited by 99 · see citing works
Application of CD27 as a marker for distinguishing human NK cell subsets
da Silva, A. B. G., Andrews, D. M., Brööks, A. G., et al. (2008) · International Immunology · doi:10.1093/intimm/dxn022 · Cited by 85 · see citing works
Phillips, J. H., & Lanier, L. L. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.161.6.1464 · Cited by 83 · see citing works
Self-citationLigand binding to Fc gamma R induces c-myc-dependent apoptosis in IL-2-stimulated NK cells.
Azzoni, L., Anegón, I., Calabretta, B., & PERUSSIA, B. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.2.491 · Cited by 71 · see citing works
The enigma of CD57+CD28– T cell expansion—anergy or activation?
Kern, F., Ode-Hakim, S., Vogt, K., Höflich, C., Reinke, P., & Volk, H. (1996) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1996.d01-635.x · Cited by 60 · see citing works
Proliferation and interleukin 5 production by CD8hiCD57+ T cells
Chong, L. K., Aicheler, R., Llewellyn‐Lacey, S., Tomašec, P., Brennan, P., & Wang, E. C. Y. (2008) · European Journal of Immunology · doi:10.1002/eji.200737687 · Cited by 58 · see citing works
Human Vγ9/Vδ2 effector memory T cells express the killer cell lectin-like receptor G1 (KLRG1)
Eberl, M., Engel, R., Aberle, S., Fisch, P., Jomaa, H., & Pircher, H. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0204096 · Cited by 38 · see citing works
Self-citationTilden, A. B., Grossi, C. E., Itoh, K., Cloud, G. A., Dougherty, P. A., & Balch, C. M. (1986) · PubMed · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lopez-Vergès, S., Milush, J. M., Schwartz, B. S., Pando, M. J., Jarjoura, J., York, V. A., Houchins, J. P., Miller, S., Kang, S.-M., Norris, P. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110900108 · Cited by 822 · see citing works
Self-citationSolana, R., Tarazona, R., Gayoso, I., Lesur, O., Dupuis, G., & Fulop, T. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.008 · Cited by 567 · see citing works
The Role of the Immune System in Autism Spectrum Disorder
Meltzer, A., & Van de Water, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.158 · Cited by 533 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
Franceschi, C., Salvioli, S., Garagnani, P., de Eguileor, M., Monti, D., & Capri, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00982 · Cited by 290 · see citing works
Exercise and the aging immune system
Simpson, R. J., Lowder, T. W., Spielmann, G., Bigley, A. B., LaVoy, E. C., & Kunz, H. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.03.003 · Cited by 281 · see citing works
Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease
Nielsen, C. M., White, M. J., Goodier, M. R., & Riley, E. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00422 · Cited by 282 · see citing works
Pasero, C., Gravis, G., Guerin, M., Granjeaud, S., Thomassin-Piana, J., Rocchi, P., Paciencia-Gros, M., Poizat, F., Bentobji, M., Azario-Cheillan, F., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1965 · Cited by 209 · see citing works
Manser, A. R., & Uhrberg, M. (2016) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-015-1750-0 · Cited by 148 · see citing works
Effect of age and CMV on NK cell subpopulations
Campos, C., Pera, A., Sanchez-Correa, B., Alonso, C., Lopez-Fernandez, I., Morgado, S., Tarazona, R., & Solana, R. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.008 · Cited by 128 · see citing works
Lutz, C. T., Karapetyan, A., Al-Attar, A., Shelton, B. J., Holt, K. J., Tucker, J. H., & Presnell, S. R. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002732 · Cited by 118 · see citing works
Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans
Bayard, C., Lepetitcorps, H., Roux, A., Larsen, M., Fastenackels, S., Salle, V., Vieillard, V., Marchant, A., Stern, M., Boddaert, J., et al. (2016) · European Journal of Immunology · doi:10.1002/eji.201546179 · Cited by 65 · see citing works
Campos, C., López, N., Pera, A., Gordillo, J. J., Hassouneh, F., Tarazona, R., & Solana, R. (2015) · Biogerontology · doi:10.1007/s10522-015-9581-0 · Cited by 54 · see citing works
- Authors
- Lopez-Vergès, S., Milush, J. M., Pandey, S., York, V. A., Arakawa-Hoyt, J., Pircher, H., Norris, P. J., Nixon, D. F., & Lanier, L. L.
- Affiliations
- Department of Microbiology and Immunology and the Cancer Research Institute, University of California–San Francisco, San Francisco, CA;
- University of California, San Francisco (US)
- Blood Systems Research Institute (US)
- University of Freiburg (DE)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-11-11
- Volume
- 116
- Issue
- 19
- Pages
- 3865-3874
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2981540
- OpenAlex
- W2087590625
- Cited by
- 752
- References
- 50
- Citations by year
- 2026: 34 · 2025: 40 · 2024: 58 · 2023: 35 · 2022: 55 · 2021: 54 · 2020: 61 · 2019: 55 · 2018: 43 · 2017: 55 · 2016: 54 · 2015: 52 · 2014: 44 · 2013: 50 · 2012: 25
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl095470-04)
- National Heart, Lung, and Blood Institute (HL095470, R01 HL-095470, T32HL007185)
- National Institute of Allergy and Infectious Diseases (AI-068129, R01AI068129, P01AI064520, R01AI083113, AI 64520)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- CD57, natural killer cells, NK cell maturation, NK cell receptors, CD16, interferon-gamma, cytotoxicity, IL-12, IL-18, interleukin-2, NK cell proliferation, terminal differentiation, NK cell subsets
- MeSH terms
- Adult, Cell Differentiation, Cytotoxicity, Immunologic, Humans, Interferon-gamma, Killer Cells, Natural, Lymphocyte Activation, Cell Death, Receptors, IgG, Interleukin-12, CD57 Antigens, CD56 Antigen, Interleukin-18, Gene Expression Profiling, Cell Proliferation, GPI-Linked Proteins, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
