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* Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021;
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy;
Division of Nephrology, Department of Medicine, and
Department of Pathology and Laboratory Medicine, Weill Medical College, New York, NY 10021; and
¶ Dipartimento di Medicina Sperimentale, Sezione di Istologia, and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy
Natural killer cells are important cytolytic cells in innate immunity. We have characterized human NK cells of spleen, lymph nodes, and tonsils. More than 95% of peripheral blood and 85% of spleen NK cells are CD56dimCD16+ and express perforin, the natural cytotoxicity receptors (NCRs) NKp30 and NKp46, as well as in part killer cell Ig-like receptors (KIRs). In contrast, NK cells in lymph nodes have mainly a CD56brightCD16- phenotype and lack perforin. In addition, they lack KIRs and all NCR expression, except low levels of NKp46. The NK cells of tonsils also lack perforin, KIRs, NKp30, and CD16, but partially express NKp44 and NKp46. Upon IL-2 stimulation, however, lymph node and tonsilar NK cells up-regulate NCRs, express perforin, and acquire cytolytic activity for NK-sensitive target cells. In addition, they express CD16 and KIRs upon IL-2 activation, and therefore display a phenotype similar to peripheral blood NK cells. We hypothesize that IL-2 can mobilize the NK cells of secondary lymphoid tissues to mediate natural killing during immune responses. Because lymph nodes harbor 40% and peripheral blood only 2% of all lymphocytes in humans, this newly characterized perforin- NK cell compartment in lymph nodes and related tissues probably outnumbers perforin+ NK cells. These results also suggest secondary lymphoid organs as a possible site of NK cell differentiation and self-tolerance acquisition.
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A. Munitz, I. Bachelet, R. Eliashar, A. Moretta, L. Moretta, and F. Levi-Schaffer The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF, and eotaxin on human peripheral blood eosinophils Blood, March 1, 2006; 107(5): 1996 - 2003. [Abstract] [Full Text] [PDF]
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S. Chen, H. Kawashima, J. B. Lowe, L. L. Lanier, and M. Fukuda Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment J. Exp. Med., December 19, 2005; 202(12): 1679 - 1689. [Abstract] [Full Text] [PDF]
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A. Poggi, C. Prevosto, A.-M. Massaro, S. Negrini, S. Urbani, I. Pierri, R. Saccardi, M. Gobbi, and M. R. Zocchi Interaction between Human NK Cells and Bone Marrow Stromal Cells Induces NK Cell Triggering: Role of NKp30 and NKG2D Receptors J. Immunol., November 15, 2005; 175(10): 6352 - 6360. [Abstract] [Full Text] [PDF]
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P. Schierloh, N. Yokobori, M. Aleman, R. M. Musella, M. Beigier-Bompadre, M. A. Saab, L. Alves, E. Abbate, S. S. de la Barrera, and M. C. Sasiain Increased Susceptibility to Apoptosis of CD56dimCD16+ NK Cells Induces the Enrichment of IFN-{gamma}-Producing CD56bright Cells in Tuberculous Pleurisy J. Immunol., November 15, 2005; 175(10): 6852 - 6860. [Abstract] [Full Text] [PDF]
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J. Hanna, H. Mussaffi, G. Steuer, S. Hanna, M. Deeb, H. Blau, T. I. Arnon, N. Weizman, and O. Mandelboim Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency Blood, November 15, 2005; 106(10): 3465 - 3473. [Abstract] [Full Text] [PDF]
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P. S. Woll, C. H. Martin, J. S. Miller, and D. S. Kaufman Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity J. Immunol., October 15, 2005; 175(8): 5095 - 5103. [Abstract] [Full Text] [PDF]
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M. I. Lutskiy, D. S. Beardsley, F. S. Rosen, and E. Remold-O'Donnell Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome Blood, October 15, 2005; 106(8): 2815 - 2817. [Abstract] [Full Text] [PDF]
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R. B. Mailliard, S. M. Alber, H. Shen, S. C. Watkins, J. M. Kirkwood, R. B. Herberman, and P. Kalinski IL-18-induced CD83+CCR7+ NK helper cells J. Exp. Med., October 3, 2005; 202(7): 941 - 953. [Abstract] [Full Text] [PDF]
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T. Walzer, M. Dalod, S. H. Robbins, L. Zitvogel, and E. Vivier Natural-killer cells and dendritic cells: "l'union fait la force" Blood, October 1, 2005; 106(7): 2252 - 2258. [Abstract] [Full Text] [PDF]
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A. Fuchs, M. Cella, T. Kondo, and M. Colonna Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44 Blood, September 15, 2005; 106(6): 2076 - 2082. [Abstract] [Full Text] [PDF]
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M. Vitale, M. D. Chiesa, S. Carlomagno, D. Pende, M. Arico, L. Moretta, and A. Moretta NK-dependent DC maturation is mediated by TNF{alpha} and IFN{gamma} released upon engagement of the NKp30 triggering receptor Blood, July 15, 2005; 106(2): 566 - 571. [Abstract] [Full Text] [PDF]
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S. Nguyen, N. Dhedin, J.-P. Vernant, M. Kuentz, A. A. Jijakli, N. Rouas-Freiss, E. D. Carosella, A. Boudifa, P. Debre, and V. Vieillard NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect Blood, May 15, 2005; 105(10): 4135 - 4142. [Abstract] [Full Text] [PDF]
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R. Biassoni, M. Fogli, C. Cantoni, P. Costa, R. Conte, G. Koopman, A. Cafaro, B. Ensoli, A. Moretta, L. Moretta, et al. Molecular and Functional Characterization of NKG2D, NKp80, and NKG2C Triggering NK Cell Receptors in Rhesus and Cynomolgus Macaques: Monitoring of NK Cell Function during Simian HIV Infection J. Immunol., May 1, 2005; 174(9): 5695 - 5705. [Abstract] [Full Text] [PDF]
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E. Marcenaro, M. D. Chiesa, F. Bellora, S. Parolini, R. Millo, L. Moretta, and A. Moretta IL-12 or IL-4 Prime Human NK Cells to Mediate Functionally Divergent Interactions with Dendritic Cells or Tumors J. Immunol., April 1, 2005; 174(7): 3992 - 3998. [Abstract] [Full Text] [PDF]
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F. Gerosa, A. Gobbi, P. Zorzi, S. Burg, F. Briere, G. Carra, and G. Trinchieri The Reciprocal Interaction of NK Cells with Plasmacytoid or Myeloid Dendritic Cells Profoundly Affects Innate Resistance Functions J. Immunol., January 15, 2005; 174(2): 727 - 734. [Abstract] [Full Text] [PDF]
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C. Munz, T. Dao, G. Ferlazzo, M. A. de Cos, K. Goodman, and J. W. Young Mature myeloid dendritic cell subsets have distinct roles for activation and viability of circulating human natural killer cells Blood, January 1, 2005; 105(1): 266 - 273. [Abstract] [Full Text] [PDF]
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S. Li, J. Xu, V. P. Makarenkova, T. Tjandrawan, J. Vakkila, T. Reichert, W. Gooding, C. F. Lagenaur, C. L. Achim, W. H. Chambers, et al. A novel epitope of N-CAM defines precursors of human adherent NK cells J. Leukoc. Biol., December 1, 2004; 76(6): 1187 - 1199. [Abstract] [Full Text] [PDF]
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I. H. Westgaard, S. F. Berg, J. T. Vaage, L. L. Wang, W. M. Yokoyama, E. Dissen, and S. Fossum Rat NKp46 activates natural killer cell cytotoxicity and is associated with Fc{varepsilon}RI{gamma} and CD3{zeta} J. Leukoc. Biol., December 1, 2004; 76(6): 1200 - 1206. [Abstract] [Full Text] [PDF]
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J. Hanna, P. Bechtel, Y. Zhai, F. Youssef, K. McLachlan, and O. Mandelboim Novel Insights on Human NK Cells' Immunological Modalities Revealed by Gene Expression Profiling J. Immunol., December 1, 2004; 173(11): 6547 - 6563. [Abstract] [Full Text] [PDF]
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 G. Ferlazzo, M. Pack, D. Thomas, C. Paludan, D. Schmid, T. Strowig, G. Bougras, W. A. Muller, L. Moretta, and C. Munz Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs PNAS, November 23, 2004; 101(47): 16606 - 16611. [Abstract] [Full Text] [PDF]
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A. Barakonyi, M. Rabot, A. Marie-Cardine, M. Aguerre-Girr, B. Polgar, V. Schiavon, A. Bensussan, and P. Le Bouteiller Cutting Edge: Engagement of CD160 by its HLA-C Physiological Ligand Triggers a Unique Cytokine Profile Secretion in the Cytotoxic Peripheral Blood NK Cell Subset J. Immunol., November 1, 2004; 173(9): 5349 - 5354. [Abstract] [Full Text] [PDF]
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L. L. Molinero, M. B. Fuertes, M. V. Girart, L. Fainboim, G. A. Rabinovich, M. A. Costas, and N. W. Zwirner NF-{kappa}B Regulates Expression of the MHC Class I-Related Chain A Gene in Activated T Lymphocytes J. Immunol., November 1, 2004; 173(9): 5583 - 5590. [Abstract] [Full Text] [PDF]
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A. Zingoni, T. Sornasse, B. G. Cocks, Y. Tanaka, A. Santoni, and L. L. Lanier Cross-Talk between Activated Human NK Cells and CD4+ T Cells via OX40-OX40 Ligand Interactions J. Immunol., September 15, 2004; 173(6): 3716 - 3724. [Abstract] [Full Text] [PDF]
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S. Sivori, M. Falco, M. D. Chiesa, S. Carlomagno, M. Vitale, L. Moretta, and A. Moretta CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: Induction of cytokine release and cytotoxicity against tumors and dendritic cells PNAS, July 6, 2004; 101(27): 10116 - 10121. [Abstract] [Full Text] [PDF]
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