Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis

• Published in: Rheumatology (Oxford, England) Vol. 47; no. 1; pp. 22 - 30
• Main Authors: Zheng, Z. H., Li, X. Y., Ding, J., Jia, J. F., Zhu, P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2008; Oxford Publishing Limited (England)
• Subjects: Adult; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Biomarkers - metabolism; Bone Marrow Cells; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Chondrocytes - cytology; Chondrocytes - immunology; Chondrocytes - metabolism; Coculture Techniques; Collagen Type II - immunology; Collagen Type II - metabolism; Collagen Type II - pharmacology; Diseases of the osteoarticular system; Dose-Response Relationship, Immunologic; Female; Humans; Immunosuppression; Inflammatory joint diseases; Interferon-gamma - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; Medical sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; Middle Aged; Rheumatoid arthritis; T lymphocyte; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - metabolism; Type II collagen; Immunosuppression; T lymphocyte; Type II collagen; Rheumatoid arthritis; Mesenchymal stem cells; Immunopathology; Chondrocyte; Stem cell; Diseases of the osteoarticular system; Reactive arthritis; Autoimmune disease; Collagen type II; Inflammatory joint disease; Spondylarthropathy; Chronic; Immunological investigation; T-Lymphocyte; Th2 lymphocyte
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kem284

Objective. Rheumatoid arthritis (RA) is a T-cell-mediated systematic disease and is usually accompanied by articular cartilage damage. In the present study, we explored the effects of bone marrow-derived mesenchymal stem cells (MSCs) and MSC-differentiated chondrocytes (MSC-chondrocytes) on the responses of antigen-specific T cells in RA to type II collagen (CII) to evaluate the potential therapeutic value of MSCs in RA treatment. Methods. The effects of both MSCs and MSC-chondrocytes on the proliferation, activation-antigen expression (CD69 and CD25) and cytokine production [interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), interleukin (IL)-10 and IL-4] of CII-reactive T cells in RA patients were investigated with the stimulation of CII or otherwise. CD3/annexin V staining was used to evaluate T-cell apoptosis in the inhibition. The role of transforming growth factor-β1 (TGF-β1) underlying the inhibition was also investigated. Results. MSCs failed to elicit positive responses of CII-reactive T cells, whereas they significantly suppressed CII-stimulated T-cell proliferation and activation-antigen expression in a dose-dependent fashion without inducing T-cell apoptosis. The inhibition was observed even after MSCs were added as late as 3 days after the initiation of stimulation. Moreover, MSCs inhibited both CD4+ and CD8+ T cells from producing IFN-γ and TNF-α, while they up-regulated the levels of IL-10 and restored the secretion of IL-4. TGF-β1 was confirmed to play a critical role in the inhibition. Throughout our study, MSC-chondrocytes shared similar properties with MSCs. Conclusion. Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.