{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:07:26Z","timestamp":1790338046826,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent studies suggested that human CD56brightCD16\u2212 NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides\/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56dimCD16+ and CD56brightCD16\u2212 NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56brightCD16\u2212 than in CD56dimCD16+ NK cells. CD57 was mostly expressed by CD56dimCD16+ NK cells. CD203a\/PC-1 expression was restricted to CD56brightCD16\u2212 NK cells. CD56brightCD16\u2212 NK cells produce ADO and inhibit autologous CD4+ T cell proliferation. Such inhibition was 1) reverted pretreating CD56brightCD16\u2212 NK cells with a CD38 inhibitor and 2) increased pretreating CD56brightCD16\u2212 NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56brightCD16\u2212 NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4+ T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38\/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56brightCD16\u2212 NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56brightCD16\u2212 NK cells act as \u201cregulatory cells\u201d through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune\/inflammatory diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1500591","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T22:30:43Z","timestamp":1434753043000},"page":"965-972","source":"Crossref","is-referenced-by-count":134,"title":["CD56brightCD16\u2212 NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation"],"prefix":"10.1093","volume":"195","author":[{"given":"Fabio","family":"Morandi","sequence":"first","affiliation":[{"name":"Laboratorio di Oncologia, Istituto Giannina Gaslini , 16148 Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto L","family":"Horenstein","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Turin , Turin 10126 ,","place":["Italy"]},{"name":"Immunologia dei Trapianti, Citt\u00e0 della Salute e della Scienza , Turin 10126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Chillemi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Turin , Turin 10126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Quarona","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Turin , Turin 10126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Pediatria II - Reumatologia, Istituto Giannina Gaslini , Genoa 16148 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Imperatori","sequence":"additional","affiliation":[{"name":"Department of Surgical and Morphological Sciences, University of Insubria , 21100 Varese ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Zanellato","sequence":"additional","affiliation":[{"name":"Department of Surgical and Morphological Sciences, University of Insubria , 21100 Varese ,","place":["Italy"]},{"name":"Department of Biotechnology and Life Sciences, University of Insubria , 21100 Varese ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Mortara","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences, University of Insubria , 21100 Varese ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Pediatria II - Reumatologia, Istituto Giannina Gaslini , Genoa 16148 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Pistoia","sequence":"additional","affiliation":[{"name":"Laboratorio di Oncologia, Istituto Giannina Gaslini , 16148 Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Malavasi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Turin , Turin 10126 ,","place":["Italy"]},{"name":"Immunologia dei Trapianti, Citt\u00e0 della Salute e della Scienza , Turin 10126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703581075800_r1","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1084\/jem.147.5.1314","article-title":"Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. 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