Vaccination with Collagen-Pulsed Immature Dendritic cells Significantly Delayed the Onset and Lessened Severity of Spontaneous Polychondritis in HLA-DQ Transgenic Mice (131.10)

Abstract

Listen

Translate article

Abstract Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of costimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. Here we report that injection of iDCs pulsed with chick type II collagen (CII) significantly delayed the onset and suppressed the severity of spontaneous polychondritis in HLA-DQ6αβ8αβ tg mice. Bone marrow derived iDCs were purified, pulsed in vitro with CII and transferred to 6 wk old HLA-DQ6αβ8αβ tg mice. Controls received either un-pulsed iDCs or PBS. Both control groups developed polyarthritis at 3.5 months as we have previously reported. However, none of the mice receiving CII-loaded iDCs displayed any clinical signs of disease until 5.5 months of age, indicating the ability of the DC vaccine to significantly delay the onset of the disease. The severity of disease in CII-pulsed iDC immunized test mice remained less than controls. Interestingly, after 6.5 months of age the incidence of polyarthritis in the CII-loaded iDC group gradually increased from 25% to 87%. Total IgG levels were elevated in the CII-loaded iDC test group. None of the mice developed significant CII-specific IgG responses, indicating that the CII-loaded iDCs were not inducing a CII specific immune response. This is the first evidence of iDC therapy controlling polychondritis and suggests that iDC vaccination may provide a novel tool in the treatment of human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.