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Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis.
Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Correspondence to: P. Zhu, Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China. E-mail: zhuping{at}fmmu.edu.cn
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Abstract |
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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-
(IFN-), tumour necrosis factor-
(TNF-), 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- and TNF-, 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.
KEY WORDS: Mesenchymal stem cells, Type II collagen, T lymphocyte, Rheumatoid arthritis, Immunosuppression
Submitted 29 April 2007;
revised version accepted 11 September 2007.
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