Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis.
Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6alphabeta8alphabeta transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6alphabeta8alphabeta transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5.5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3.5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.
Sidhu
M
M
Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, USA.
Griffiths
M M
MM
Bradley
D S
DS
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D006680:HLA Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D011081:Polychondritis, Relapsing / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D014611:Vaccination
D016207:Cytokines; D006680:HLA Antigens; D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; C109756:HLA-DQ8 antigen; D007074:Immunoglobulin G; D003094:Collagen