{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:06:27Z","timestamp":1791421587539,"version":"4.3.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2212 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\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.172.3.1455","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:36Z","timestamp":1398028116000},"page":"1455-1462","source":"Crossref","is-referenced-by-count":492,"title":["The Abundant NK Cells in Human Secondary Lymphoid Tissues Require Activation to Express Killer Cell Ig-Like Receptors and Become Cytolytic"],"prefix":"10.1093","volume":"172","author":[{"given":"Guido","family":"Ferlazzo","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, The Rockefeller University , New York, NY 10021"},{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolca","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Weill Medical College , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Lee","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, The Rockefeller University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiera","family":"Goodman","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, The Rockefeller University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Morandi","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Medical College , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Moretta","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Sezione di Istologia, and Centro di Eccellenza per le Ricerche Biomediche, Universita\u0300 degli Studi di Genova , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mu\u0308nz","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, The Rockefeller University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2026020211220655400_R1","first-page":"187","volume-title":"Adv. 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