{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:20:50Z","timestamp":1792657250553,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"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":[[2007,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Subnanomolar doses of an unaltered, naturally occurring nucleosomal histone peptide epitope, H471\u201394, when injected s.c. into lupus-prone mice, markedly prolong lifespan by generating CD4+25+ and CD8+ regulatory T cells (Treg) producing TGF-\u03b2. The induced Treg cells suppress nuclear autoantigen-specific Th and B cells and block renal inflammation. Splenic dendritic cells (DC) captured the s.c.-injected H471\u201394 peptide rapidly and expressed a tolerogenic phenotype. The DC of the tolerized animal, especially plasmacytoid DC, produced increased amounts of TGF-\u03b2, but diminished IL-6 on stimulation via the TLR-9 pathway by nucleosome autoantigen and other ligands; and those plasmacytoid DC blocked lupus autoimmune disease by simultaneously inducing autoantigen-specific Treg and suppressing inflammatory Th17 cells that infiltrated the kidneys of untreated lupus mice. Low-dose tolerance with H471\u201394 was effective even though the lupus immune system is spontaneously preprimed to react to the autoepitope. Thus, H471\u201394 peptide tolerance therapy that preferentially targets pathogenic autoimmune cells could spare lupus patients from chronically receiving toxic agents or global immunosuppressants and maintain remission by restoring autoantigen-specific Treg cells.<\/jats:p>","DOI":"10.4049\/jimmunol.178.12.7849","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:18:11Z","timestamp":1397863091000},"page":"7849-7858","source":"Crossref","is-referenced-by-count":167,"title":["Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells"],"prefix":"10.1093","volume":"178","author":[{"given":"Hee-Kap","family":"Kang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Departments of Medicine and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Departments of Medicine and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal K","family":"Datta","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Departments of Medicine and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,6,15]]},"reference":[{"key":"2025032803201448900_R1","first-page":"S69","volume-title":"Nat. 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