TY - JOUR
T1 - The histone peptide H4 71-94 alone is more effective than a cocktail of peptide epitopes in controlling lupus
T2 - Immunoregulatory mechanisms
AU - Kang, Hee Kap
AU - Chiang, Ming Yi
AU - Liu, Michael
AU - Ecklund, Diane
AU - Datta, Syamal K.
N1 - Funding Information:
Acknowledgements This work was supported by grants from the National Institutes of Health (R37-AR39157 and RO1-AI41985) and Solovy Arthritis Research Society.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - DC
KW - Systemic lupus erythematosus
KW - T cells
KW - autoimmunity
KW - peptides
KW - tolerance
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U2 - 10.1007/s10875-010-9504-4
DO - 10.1007/s10875-010-9504-4
M3 - Article
C2 - 21287397
AN - SCOPUS:79961173769
SN - 0271-9142
VL - 31
SP - 379
EP - 394
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 3
ER -