{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:07:24Z","timestamp":1791896844331,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"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":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We investigated the capacity of CD25+ T regulatory cells (Treg) to modulate T cell responses to nickel, a common cause of allergic contact dermatitis. CD4+ T cells isolated from the peripheral blood of six healthy, nonallergic individuals showed a limited capacity to proliferate in response to nickel in vitro, but responsiveness was strongly augmented (mean increment \u00b1 SD, 240 \u00b1 60%) when cells were depleted of CD25+ Treg. Although CD25+ Treg were anergic to nickel, a small percentage up-regulated membrane CTLA-4 upon nickel exposure. CD25+ Treg strongly and dose-dependently inhibited nickel-specific activation of CD25\u2212 T lymphocytes in coculture experiments in a cytokine-independent, but cell-to-cell contact-dependent, manner. Approximately 30% of circulating CD25+ Treg expressed the cutaneous lymphocyte-associated Ag (CLA), and CLA+CD25+ Treg were more efficient than CLA\u2212CD25+ cells in suppressing nickel responsiveness of CD25\u2212 T cells. The site of a negative patch test in response to nickel showed an infiltrate of CD4+CLA+ cells and CD25+ cells, which accounted for \u223c20% of the total T cells isolated from the tissue. Skin-derived T cells suppressed nickel-specific responses of peripheral blood CD25\u2212 T cells. In addition, 60 \u00b1 14% of peripheral blood CD25+ Treg expressed the chemokine receptor CCR7 and strongly inhibited naive T cell activation in response to nickel. Finally, CD25+ T cells isolated from peripheral blood of nickel-allergic patients showed a limited or absent capacity to suppress metal-specific CD4+ and CD8+ T cell responses. The results indicates that in healthy individuals CD25+ Treg can control the activation of both naive and effector nickel-specific T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.171.11.5760","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T01:32:01Z","timestamp":1398043921000},"page":"5760-5768","source":"Crossref","is-referenced-by-count":175,"title":["Human CD25+ Regulatory T Cells Maintain Immune Tolerance to Nickel in Healthy, Nonallergic Individuals"],"prefix":"10.1093","volume":"171","author":[{"given":"Andrea","family":"Cavani","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Nasorri","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ottaviani","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sebastiani","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"De Pita\u0300","sequence":"additional","affiliation":[{"name":"Laboratory of Allergology and Clinical Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampiero","family":"Girolomoni","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]},{"name":"Second Division of Dermatology, Istituto Dermopatico dell\u2019Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,12,1]]},"reference":[{"key":"2025032708434896000_R1","first-page":"733","volume-title":"Curr. 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