TGF-β1 Transduced Mesenchymal Stem Cells Have Profound Modulatory Effects on DCs and T Cells.
BACKGROUND
Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling.


OBJECTIVE
To evaluate the interaction of TGF-β1 engineered MSCs with T cells and dendritic cells (DCs) and their modulatory effect on the immune response.


METHODS
MSCs and DCs were generated from bone marrow of Balb/c mice and T cells were generated from mice lymph nodes. TGF-β1 expressing lentiviruses were used for MSCs transduction, and then these engineered MSCs were co-cultured with T cells and DCs. T cells proliferation and cytokines release and also DCs maturation, TNF-α release, and stimulation of allogeneic T cells were evaluated.


RESULTS
T cells proliferation and IFN-γ release were suppressed by TGF-β1/MSCs while IL-4 secretion was enhanced. Co-cultured DCs with TGF-β1/MSCs showed reduced expression of CD40, CD86, and MHC II and also lower level of TNF-α secretion. Co-cultured DCs could also induce lower levels of allogeneic T cells proliferation and IFN-γ release in comparison to control DCs.


CONCLUSIONS
Engineered TGF-β1/MSC cells showed collaborative immune suppressive functions between TGF-β1 and MSCs to modulate T cells and DCs immune responses. We therefore suggest that TGF-β1/MSC cells could provide a promising tool for treatment of clinical conditions such as organ transplantation, GVHD, and autoimmune disorders.
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Saeed
S
Daneshmandi
Mohammad Hossein
MH
Karimi
Ali Akbar
AA
Pourfathollah
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma