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Journal of Immunology Research
Volume 2015 (2015), Article ID 834085, 15 pages
http://dx.doi.org/10.1155/2015/834085
Research Article

DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice

1JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea
2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of Korea
3Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea

Received 28 January 2015; Revised 15 April 2015; Accepted 27 April 2015

Academic Editor: Patrizia Rovere-Querini

Copyright © 2015 Jun-Eui Park et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the combination therapy. CD4+Foxp3+ Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells decreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of interferon-γ (IFN-γ) and IL-17 with little influence on the IL-4 secretion in the mixed leukocyte reaction. These results imply that the combination therapy with low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg population and suppresses antigen-specific Th1/Th17 immunity, rather than initiating Th1 to Th2 immune deviation. Our findings provide a better understanding of the DC therapy in combination with MTX for the treatment of patients with rheumatoid arthritis (RA).