Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
TGF--Induced CD4CD25Foxp3 Regulatory T Cells Suppress Bone Erosion in Collagen-Induced Arthritis through Restraining the Osteoclastogenesis.
Kong3, NIng, Yang2, Ziyan, Wang3, Julie, Park3, Ryan, Dagliyan3, Grant, Conti3, Peter S., Zou1, Hejian
It is well-known that osteoclasts are responsible for the bone destruction in rheumatoid arthritis (RA) and collagen induced arthritis (CIA). Previous study has demonstrated that activated natural CD4+CD25+ regulatory T cells (nTregs) can inhibit osteoclastogenesis and CIA in a factor receptor activator of NF-kB ligand (RANKL) dependent pathway by blocking osteoclast differentiation from osteoclast precursors (OCP). Since we and other groups have identified that TGF-b-induced CD4+CD25+Foxp3+ regulatory T cells (iTregs) have the similar phenotypic and functional characteristics as nTregs, here we try to learn if iTregs also have the suppressive capacity on osteoclastogenesis and CIA.
In vitro, osteoclasts were induced from bone-marrow cells with RANKL and macrophage colony-stimulating factor (M-CSF). Naive CD4+ cells were isolated from splenocytes of normal DBA1/J mice and stimulated with anti-CD3/CD28 coated beads with IL-2 (Tcon) or IL-2+TGF-b (iTregs) for five days. On day 0, Tcon and iTregs were added to cultures for the induction of osteoclasts formation at different ratios in the presence of anti-CD3 monoclonal antibody. Osteoclast formation was determined by staining with tartrate-resistant acid phosphatase (TRAP), identified and counted by microscopes. In vivo, 3×106 iTregs were adaptively transferred to DBA1/J mice on d14 after immunization with CFA and bovine CII. The prevalence and severity of CIA mice were monitored every other day. After four-week transfer, mice accepted CT scanner on joints. The histological analysis of joints was performed and joints were stained for the identification of osteoclasts.
Addition of 10% of iTregs almost completely suppressed osteoclast formation in cultures compared with addition of similar doses of Tcon cells. Addition of anti-TGF-b or anti-IL-10 antibody to cultures cannot abolish the suppressive activities and cell-contact was required for the suppressive effect. In addition, CIA mice received iTregs have a significant lower prevalence and clinic scores than mice received Tcon cells or no cells. Of note, CT scanner showed that the joints of CIA mice received iTregs had much less bone erosion than other two groups. Accordingly, histological analysis revealed that the joints in CIA mice received iTregs had much less osteoclasts than that in mice received Tcon cells or CIA models.
iTregs can inhibit osteoclastogenesis in vitro and in vivo, and eventually suppress bone erosion in CIA diseases. This study implicates that manipulation of iTregs may have a therapeutic effect on rheumatoid arthritis and other autoimmune diseases.
To cite this abstract, please use the following information:
Kong, NIng, Yang, Ziyan, Wang, Julie, Park, Ryan, Dagliyan, Grant, Conti, Peter S., et al; TGF--Induced CD4CD25Foxp3 Regulatory T Cells Suppress Bone Erosion in Collagen-Induced Arthritis through Restraining the Osteoclastogenesis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1499