Mesenchymal stem cells induce apoptosis of activated T cells

Plumas, Joël; Chaperot, Laurence; Mj, Richard; Jp, Molens; Bensa, Jean‐Claude; Mc, Favrot

doi:10.1038/sj.leu.2403871

Cited by 292 publications

(220 citation statements)

References 20 publications

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“…As expected, third party PB-MNCs that were stimulated or not stimulated with PHA were highly immunogenic to responder T-cells (allogeneic PB-MNCs PI=4.24, PHA-treated allogeneic PB-MNCs PI= 4.5). Inhibition of Tcell proliferation were seen with both irradiated and nonirradiated MSCs as reported before [21].…”

Section: Immunogenicity Of Human Esc-derived Mscssupporting

confidence: 78%

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Trivedi

Hematti

2008

Experimental Hematology

176

159

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Objective-We have previously shown the simultaneous generation of CD73+ mesenchymal stromal cells (MSCs) along with CD34+ hematopoietic cells from human embryonic stem cells (ESCs) when they are co-cultured with OP9 murine stromal cells. We investigated whether MSCs can be derived from human ESCs without co-culturing with OP9 cells, and if such cells exhibit immunological properties similar to MSCs derived from adult human bone marrow (BM).Materials and Methods-Our starting populations were undifferentiated ESCs cultured on matrigel-coated plates without feeder cells. The differentiated fibroblast-looking cells were tested for expression of MSC markers and their potential for multi-lineage differentiation. We investigated surface expression of HLA molecules on these MSCs before and after treatment with interferon gamma (IFN-γ). We also tested the proliferative response of T-lymphocytes towards MSCs and the effects of MSCs in mixed lymphocyte reaction (MLR) assays. Conclusions-MSCs can be derived from human ESCs without feeder cells. These human ESCderived MSCs have cell surface markers, differentiation potentials, and immunological properties in vitro that are similar to adult BM-derived MSCs. Results-We

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Section: Immunogenicity Of Human Esc-derived Mscssupporting

confidence: 78%

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Trivedi

Hematti

2008

Experimental Hematology

176

159

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“…One other established mechanism of human MSC-mediated suppression is IDO activity upregulation. IDO activation is induced by IFN-γ, and IDO catalyses the conversion of tryptophan into kynurenine [26,27]. Activation of IDO thus causes tryptophan depletion, resulting in reduced lymphocyte proliferation [28].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells

et al. 2009

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Aims/hypothesis Displaying immunomodulatory capacities, mesenchymal stem cells (MSCs) are considered as beneficial agents for autoimmune diseases. The aim of this study was to examine the ability of MSCs to prevent autoimmune diabetes in the NOD mouse model. Methods Prevention of spontaneous insulitis or of diabetes was evaluated after a single i.v. injection of MSCs in 4-week-old female NOD mice, or following the coinjection of MSCs and diabetogenic T cells in irradiated male NOD recipients, respectively. The frequency of CD4 + FOXP3 + cells and Foxp3 mRNA levels in the spleen of male NOD recipients were also quantified. In vivo cell homing was assessed by monitoring 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled T cells or MSCs. In vitro, cell proliferation and cytokine production were assessed by adding graded doses of irradiated MSCs to insulin B9-23 peptide-specific T cell lines in the presence of irradiated splenocytes pulsed with the peptide. Results MSCs reduced the capacity of diabetogenic T cells to infiltrate pancreatic islets and to transfer diabetes. This protective effect was not associated with the modification of diabetogenic T cell homing, but correlated with a preferential migration of MSCs to pancreatic lymph nodes. While injection of diabetogenic T cells resulted in a decrease in levels of FOXP3 + regulatory T cells, this decrease was inhibited by MSC co-transfer. Moreover, MSCs were able to suppress both allogeneic and insulin-specific proliferative responses in vitro. This suppressive effect was associated with the induction of IL10-secreting FOXP3 + T cells. Conclusions/interpretation MSCs prevent autoimmune beta cell destruction and subsequent diabetes by inducing regulatory T cells. MSCs may thus offer a novel cell-based approach for the prevention of autoimmune diabetes and for islet cell transplantation.

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“…MSCs express indoleamine 2,3-dioxygenase (IDO)-an immune regulatory enzyme that catalyses the degradation of tryptophan via the kynurenine pathway-and exhibit functional IDO activity and IDO-dependent apoptotic effects on allogeneic human T cells upon stimulation with IFN-γ (Meisel et al, 2004;Plumas et al, 2005). In vivo in mice with EAE, transplanted syngeneic MSCs prevent relapses and promote myelin repair via an IFN-γ-dependent mechanism that induces IDO in CD11c + DCs and leads to the inhibition of antigen reactivity and disease spread (Matysiak et al, 2008(Matysiak et al, , 2011.…”

Section: Paracrine Signalingmentioning

confidence: 99%

“…Data in Table 1 are in part summarized in (Chamberlain et al, 2008;Hall et al, 2006;Martino and Pluchino 2006;Pluchino et al, 2009b;Rojewski et al, 2008;Uccelli et al, 2008;Yuan et al, 2011). (Cusimano et al, 2012;Jaderstad et al, 2010) aracrine IDO-kynurenine MSCs (h) T cells, DCs T cell apoptosis, inhibition of antigen presentation (Lanz et al, 2010;Matysiak et al, 2008Matysiak et al, , 2011Meisel et al, 2004;Plumas et al, 2005 Bonnamain et al, 2012;Chabannes et al, 2007;Moll et al, 2011) Paracrine VEGF NPCs Microglia/macrophages Inhibition of microglial activation, proliferation and phagocytosis (Horie et al, 2011;Kim et al, 2009a;Mosher et al, 2012) Paracrine LIF NPCs Th17 cells Inhibition of Th17 cell differentiation (Cao et al, 2011;Horie et al, 2011;Kim et al, 2009a;Mosher et al, 2012) Paracrine Galectins MSCs/NPCs T cells Inhibition of T cell proliferation (Gieseke et al, 2010;Sioud 2011;Yamane et al, 2010Yamane et al, , 2011 Endocrine/Paracrine TSG-6 MSCs Macrophages Inhibition of macrophage activation, proliferation and phagocytosis (Fisher-Shoval et al, 2012;Lee et al, 2009;Roddy et al, 2011) EVs miR transfer MSCs/NPCs Multiple Post-transcriptional regulation (Bruno et al, 2009;Chen et al, 2010;…”

mentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

110

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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Mesenchymal stem cells induce apoptosis of activated T cells

Cited by 292 publications

References 20 publications

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells

How stem cells speak with host immune cells in inflammatory brain diseases

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