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The Histone Peptide H471–94 Alone Is More Effective than a Cocktail of Peptide Epitopes in Controlling Lupus: Immunoregulatory Mechanisms

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Abstract

Tolerance therapy with nucleosomal histone peptides H471–94, H416–39, or H1′22–42 controls disease in lupus-prone SNF1 mice. It would be clinically important to determine whether a cocktail of the above epitopes would be superior. Herein, we found that compared with cocktail peptides, H471–94 monotherapy more effectively delayed nephritis onset, prolonged lifespan, diminished immunoglobulin G autoantibody levels, reduced autoantigen-specific Th1 and Th17 responses and frequency of TFH cells in spleen and the helper ability of autoimmune T cells to B cells, by inducing potent CD8 Treg cells. H471–94 therapy was superior in “tolerance spreading,” suppressing responses to other autoepitopes, nucleosomes, and ribonucleoprotein. We also developed an in vitro assay for therapeutic peptides (potentially in humans), which showed that H471–94, without exogenous transforming growth factor (TGF)-β, was efficient in inducing stable CD4+CD25+Foxp3+ T cells by decreasing interleukin 6 and increasing TGF-β production by dendritic cells that induced ALK5-dependent Smad-3 phosphorylation (TGF-β signal) in target autoimmune CD4+ T cells.

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Abbreviations

Treg:

regulatory T cell

LAP:

latency associated peptide

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Acknowledgements

This work was supported by grants from the National Institutes of Health (R37-AR39157 and RO1-AI41985) and Solovy Arthritis Research Society.

Flow cytometry was performed at the Northwestern University Interdepartmental Immunobiology Flow Cytometry Core Facility.

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Authors and Affiliations

  1. Division of Rheumatology, Departments of Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron St. McGaw # M300, Chicago, IL, 60611, USA

    Hee-Kap Kang, Ming-Yi Chiang, Michael Liu, Diane Ecklund & Syamal K. Datta

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  1. Hee-Kap Kang
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  2. Ming-Yi Chiang
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  3. Michael Liu
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Correspondence to Syamal K. Datta.

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Kang, HK., Chiang, MY., Liu, M. et al. The Histone Peptide H471–94 Alone Is More Effective than a Cocktail of Peptide Epitopes in Controlling Lupus: Immunoregulatory Mechanisms. J Clin Immunol 31, 379–394 (2011). https://doi.org/10.1007/s10875-010-9504-4

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