Abstract
Tolerance therapy with nucleosomal histone peptides H4 71-94, H4 16-39, 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, H4 71-94 monotherapy more effectively delayed nephritis onset, prolonged lifespan, diminished immunoglobulin G autoantibody levels, reduced autoantigen-specific Th1 and Th17 responses and frequency of T FH cells in spleen and the helper ability of autoimmune T cells to B cells, by inducing potent CD8 Treg cells. H4 71-94 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 H4 71-94, 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.
Original language | English (US) |
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Pages (from-to) | 379-394 |
Number of pages | 16 |
Journal | Journal of Clinical Immunology |
Volume | 31 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2011 |
Funding
Acknowledgements This work was supported by grants from the National Institutes of Health (R37-AR39157 and RO1-AI41985) and Solovy Arthritis Research Society.
Keywords
- DC
- Systemic lupus erythematosus
- T cells
- autoimmunity
- peptides
- tolerance
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology