{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:57:50Z","timestamp":1790006270215,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"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":[[2007,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4+CD25+Foxp3+ and CD4+CD25\u2212TGF-\u03b21+ adaptive Tregs. These cells were CD62Llow and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62Lhigh counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.179.8.5191","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:19:36Z","timestamp":1397848776000},"page":"5191-5203","source":"Crossref","is-referenced-by-count":45,"title":["Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25\u2212 TGF-\u03b21+ Adaptive Regulatory T Cells"],"prefix":"10.1093","volume":"179","author":[{"given":"Ruobing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subha","family":"Karumuthil-Melethil","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bellur S","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Holterman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenthamarakshan","family":"Vasu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Illinois , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,10,15]]},"reference":[{"key":"2026012809243646400_R1","first-page":"233","volume-title":"Annu. 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