Murine bone marrow mesenchymal stem cells cause mature dendritic cells to promote T-cell tolerance.
Bone mesenchymal stem cells (BMSC) are attractive not only in regenerative medicine, but also for the treatment of autoimmune diseases and graft-versus-host disease. BMSC also play a role in enabling alloantigen tolerance. An in-depth mechanistic understanding of this phenomenon of tolerance could lead to novel cell-based therapies for autoimmune disease. We demonstrate here that co-culture of mature dendritic cells (DC) with BMSC in a transwell system (BMSC-DC) downregulated expression of the maturation marker, CD83 and CD80/86 co-stimulatory molecules on DC, while increasing their endocytic activity. This resulted in defective antigen presentation and co-stimulatory capacity of mature DC. Functionally, BMSC-DC have impaired T-cell stimulatory activity in a mixed lymphocyte reaction and orchestrate a shift from predominantly pro-inflammatory T-helper (Th)-1 to anti-inflammatory Th2 cells. While the expression of MHC II, CD80 and CD86 were upregulated on BMSC co-cultured with DC, these BMSC lacked the ability to stimulate T-cell proliferation. Taken together, these data suggest that the interaction between BMSC and DC modulates the immunoregulatory function of these cells in a coordinated manner, effectively skewing the immune response towards T-cell tolerance.
Wang
Q
Q
Department of Neurobiology, Harbin Medical University Provincial Key Lad of Neurobiology, Harbin, Heilongjiang, China.
Sun
B
B
Wang
D
D
Ji
Y
Y
Kong
Q
Q
Wang
G
G
Wang
J
J
Zhao
W
W
Jin
L
L
Li
H
H
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D015870:Gene Expression; D005802:Genes, MHC Class II; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen