Superior molecularly altered influenza virus hemagglutinin peptide 308-317 inhibits collagen-induced arthritis by inducing CD4+ Treg cell expansion

Objective To investigate the inhibitory effect and possible mechanism of a novel influenza virus hemagglutinin 308317 peptide (altered HA308317 peptide) in collagen-induced arthritis (CIA). Methods CIA was induced in DBA/1 mice by immunization with type II collagen (CII). Altered HA308317 peptide, wild HA308317 peptide, wild CII263272 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. Results Intranasal administration of wild CII263272 peptide, wild HA308317 peptide, or altered HA308317 peptide could significantly ameliorate CIA, but altered HA308317 peptide showed greater therapeutic effects than wild CII263272 peptide and wild HA308317 peptide. The effect of altered HA308317 peptide was associated with a substantial decrease in production of interleukin-17 (IL-17) and interferon-? (IFN?) and with a marked increase in production of IL-10 and transforming growth factor beta, both in serum and in supernatants from splenocytes treated with altered HA308317 peptide. Both the number and function of CD4+ Treg cells were significantly up-regulated by altered HA308317 peptide, with a decreased induction of Th1 cells (CD4+IFN?+) and Th17 cells (CD4+IL-17+). Adoptive transfer of CD4+CD25+ T cells from altered HA308317 peptidetreated mice resulted in greater suppressive capacity in ameliorating CIA severity than did adoptive transfer of CD4+CD25+ T cells from wild HA308317 peptidetreated, wild CII263272 peptidetreated, or irrelevant peptidetreated mice. Conclusion Intranasal administration of altered HA308317 peptide potently suppressed the severity of CIA by increasing the number and function of CD4+ Treg cells, suggesting that altered HA308317 peptide might be a promising candidate for treatment of rheumatoid arthritis.