{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:01:24Z","timestamp":1790823684605,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"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":[[2002,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we show that binding to autologous dendritic cells (DC) induces a calcium influx in NK cells, followed by activation of the calcium-calmodulin kinase II (CAMKII), release of perforin and granzymes, and IFN-\u03b3 secretion. CAMKII is induced via LFA-1: indeed, oligomerization of LFA-1 leads to CAMKII induction in NK cells. Moreover, release of lytic enzymes and cytotoxic activity is strongly reduced by masking LFA-1 or by adding CAMKII inhibitors such as KN62 and KN93, at variance with the inactive compound KN92. NK cell-mediated lysis of DC and IFN-\u03b3 release by NK cells upon NK\/DC contact are inhibited by exogenous HIV-1 Tat: the protein blocks calcium influx and impairs CAMKII activation elicited via LFA-1 in NK cells, eventually inhibiting degranulation. Experiments performed with synthetic, overlapping Tat-derived peptides showed that the C-terminal domain of the protein is responsible for inhibition. Finally, both KN62 and Tat reduced the extension of NK\/DC contacts, possibly affecting NK cell granule polarization toward the target. These data provide evidence that exogenous Tat inhibits NK cell activation occurring upon contact with DC: this mechanism might contribute to the impairment of natural immunity in HIV-1 infection.<\/jats:p>","DOI":"10.4049\/jimmunol.168.1.95","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:25:14Z","timestamp":1398032714000},"page":"95-101","source":"Crossref","is-referenced-by-count":65,"title":["NK Cell Activation by Dendritic Cells Is Dependent on LFA-1-Mediated Induction of Calcium-Calmodulin Kinase II: Inhibition by HIV-1 Tat C-Terminal Domain"],"prefix":"10.1093","volume":"168","author":[{"given":"Alessandro","family":"Poggi","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Institute for Cancer Research , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Carosio","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute for Cancer Research , Genoa ,","place":["Italy"]},{"name":"Laboratory of Tumor Immunology, Scientific Institute San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia Maria","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute for Cancer Research , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Fortis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Division of Infectious Diseases, Centro San Luigi , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tambussi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Division of Infectious Diseases, Centro San Luigi , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Dell\u2019Antonio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Scientific Institute San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dal Cin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Scientific Institute San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rubartelli","sequence":"additional","affiliation":[{"name":"Unit of Protein Biology, National Institute for Cancer Research , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Raffaella","family":"Zocchi","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Immunology, Scientific Institute San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,1,1]]},"reference":[{"key":"2026020208150520200_R1","first-page":"187","volume-title":"Adv. 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