We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of\ncollagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy\nwith smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and\ntype II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose\nMTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the\ncombination therapy. CD4+Foxp3+ Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells\ndecreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of\ninterferon-
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