Murine Bone Marrow Mesenchymal Stem Cells Cause Mature Dendritic Cells to Promote T-Cell Tolerance

    loading  Checking for direct PDF access through Ovid


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.

Related Topics

    loading  Loading Related Articles