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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.
Rheumatology (Oxford). 2008 Jan; 47(1):22-30.R

Abstract

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.

Authors+Show Affiliations

Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18077486

Citation

Zheng, Z H., et al. "Allogeneic Mesenchymal Stem Cell and Mesenchymal Stem Cell-differentiated Chondrocyte Suppress the Responses of Type II Collagen-reactive T Cells in Rheumatoid Arthritis." Rheumatology (Oxford, England), vol. 47, no. 1, 2008, pp. 22-30.
Zheng ZH, Li XY, Ding J, et al. Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. Rheumatology (Oxford). 2008;47(1):22-30.
Zheng, Z. H., Li, X. Y., Ding, J., Jia, J. F., & Zhu, P. (2008). Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. Rheumatology (Oxford, England), 47(1), 22-30.
Zheng ZH, et al. Allogeneic Mesenchymal Stem Cell and Mesenchymal Stem Cell-differentiated Chondrocyte Suppress the Responses of Type II Collagen-reactive T Cells in Rheumatoid Arthritis. Rheumatology (Oxford). 2008;47(1):22-30. PubMed PMID: 18077486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. AU - Zheng,Z H, AU - Li,X Y, AU - Ding,J, AU - Jia,J F, AU - Zhu,P, PY - 2007/12/14/pubmed PY - 2008/1/11/medline PY - 2007/12/14/entrez SP - 22 EP - 30 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 47 IS - 1 N2 - 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. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/18077486/Allogeneic_mesenchymal_stem_cell_and_mesenchymal_stem_cell_differentiated_chondrocyte_suppress_the_responses_of_type_II_collagen_reactive_T_cells_in_rheumatoid_arthritis_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kem284 DB - PRIME DP - Unbound Medicine ER -