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

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).

• Authors: Jun-Eui Park, Jinah Jang, Ji-Hye Choi, Mi-Sun Kang, Yun-Ju Woo, Young-Rim Seong, Chan-Bum Choi, Hye-Soon Lee, Sang-Cheol Bae, Yong-Soo Bae
• Journal: Journal of immunology research (J Immunol Res) Vol. 2015 Pg. 834085 ( 2015) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 26221616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Immunosuppressive Agents
• Methotrexate

Topics

• Animals
• Antigens, Surface (metabolism)
• Arthritis, Experimental (immunology, metabolism, pathology, therapy)
• Coculture Techniques
• Dendritic Cells (immunology, metabolism)
• Disease Models, Animal
• Female
• Immune Tolerance
• Immunophenotyping
• Immunosuppression Therapy
• Immunosuppressive Agents (administration & dosage)
• Immunotherapy, Adoptive
• Lymphoid Tissue (immunology, metabolism)
• Methotrexate (administration & dosage)
• Mice
• Phenotype
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Th1 Cells (immunology, metabolism)
• Th17 Cells (immunology, metabolism)