Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity

Li Zhang, Anne M. Bertucci, Rosalind Ramsey-Goldman, Elizabeth Randall Harsha-Strong, Richard K. Burt, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Low-dose tolerance therapy with nucleosomal histone peptide epitopes blocks lupus disease in mouse models, but effect in humans is unknown. Herein, we found that CD4+CD25highFoxP3+ or CD4+CD45RA+FoxP3low T-cells, and CD8+CD25+FoxP3+ T-cells were all induced durably in PBMCs from inactive lupus patients and healthy subjects by the histone peptide/s themselves, but in active lupus, dexamethasone or hydroxychloroquine unmasked Treg-induction by the peptides. The peptide-induced Treg depended on TGFβ/ALK-5/pSmad 2/3 signaling, and they expressed TGF-β precursor LAP. Lupus patients' sera did not inhibit Treg induction. The peptide epitope-induced T cells markedly suppressed type I IFN related gene expression in lupus PBMC. Finally, the peptide epitopes suppressed pathogenic autoantibody production by PBMC from active lupus patients to baseline levels by additional mechanisms besides Treg induction, and as potently as anti-IL6 antibody. Thus, low-dose histone peptide epitopes block pathogenic autoimmune response in human lupus by multiple mechanisms to restore a stable immunoregulatory state.

Original languageEnglish (US)
Pages (from-to)365-378
Number of pages14
JournalClinical Immunology
Volume149
Issue number3 PB
DOIs
StatePublished - Dec 2013

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Keywords

  • Autoimmunity
  • Human
  • Peptide epitopes
  • Systemic lupus erythematosus
  • T cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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