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

摘要

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-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), 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-beta1 (TGF-beta1) 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-gamma and TNF-alpha, while they up-regulated the levels of IL-10 and restored the secretion of IL-4. TGF-beta1 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.