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


CONCLUSIONS
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.
Zheng
Z H
ZH
Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Li
X Y
XY
Ding
J
J
Jia
J F
JF
Zhu
P
P
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D024043:Collagen Type II / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D024043:Collagen Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma