Drs. J. Sun and R. Li contributed equally to this work.
Superior molecularly altered influenza virus hemagglutinin peptide 308–317 inhibits collagen-induced arthritis by inducing CD4+ Treg cell expansion
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2158–2168, July 2012
How to Cite
Sun, J., Li, R., Guo, J., Jia, Y., Sun, X., Liu, Y., Li, Y., Huang, F., Lu, L. and Li, Z. (2012), Superior molecularly altered influenza virus hemagglutinin peptide 308–317 inhibits collagen-induced arthritis by inducing CD4+ Treg cell expansion. Arthritis & Rheumatism, 64: 2158–2168. doi: 10.1002/art.34372
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 9 JAN 2012 01:37PM EST
- Manuscript Accepted: 3 JAN 2012
- Manuscript Received: 17 NOV 2010
- National Major Scientific and Technological Specialized Project. Grant Number: 2009ZX09103-746
- National Basic Research Program of China. Grant Number: 973 Program, 2010CB 529100
To investigate the inhibitory effect and possible mechanism of a novel influenza virus hemagglutinin 308–317 peptide (altered HA308–317 peptide) in collagen-induced arthritis (CIA).
CIA was induced in DBA/1 mice by immunization with type II collagen (CII). Altered HA308–317 peptide, wild HA308–317 peptide, wild CII263–272 peptide, and irrelevant peptide were administered intranasally beginning at arthritis onset. Clinical and histologic scores were assessed, and cytokine levels were determined in the serum or in supernatants from splenocytes. Characteristics of T cell subsets in response to different peptides were analyzed both in vivo and in vitro.
Intranasal administration of wild CII263–272 peptide, wild HA308–317 peptide, or altered HA308–317 peptide could significantly ameliorate CIA, but altered HA308–317 peptide showed greater therapeutic effects than wild CII263–272 peptide and wild HA308–317 peptide. The effect of altered HA308–317 peptide was associated with a substantial decrease in production of interleukin-17 (IL-17) and interferon-γ (IFNγ) and with a marked increase in production of IL-10 and transforming growth factor β, both in serum and in supernatants from splenocytes treated with altered HA308–317 peptide. Both the number and function of CD4+ Treg cells were significantly up-regulated by altered HA308–317 peptide, with a decreased induction of Th1 cells (CD4+IFNγ+) and Th17 cells (CD4+IL-17+). Adoptive transfer of CD4+CD25+ T cells from altered HA308–317 peptide–treated mice resulted in greater suppressive capacity in ameliorating CIA severity than did adoptive transfer of CD4+CD25+ T cells from wild HA308–317 peptide–treated, wild CII263–272 peptide–treated, or irrelevant peptide–treated mice.
Intranasal administration of altered HA308–317 peptide potently suppressed the severity of CIA by increasing the number and function of CD4+ Treg cells, suggesting that altered HA308–317 peptide might be a promising candidate for treatment of rheumatoid arthritis.