Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide

Krampera, Mauro; Glennie, Sarah; Dyson, Julian; Scott, Diane; Laylor, R.; Simpson, Elizabeth; Dazzi, Francesco

doi:10.1182/blood-2002-07-2104

Cited by 1,462 publications

(1,319 citation statements)

References 34 publications

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“…However, only in 2002 has it been clearly demonstrated that human MSC (i) could inhibit proliferation of T cells that had either been cultured in mixed lymphocyte reactions (MLR) or stimulated by polyclonal activators [13], and (ii) upon in vivo infusion, could prolong skin engraftment in nonhuman primates [12]. Krampera et al further demonstrated that the anti-proliferative activity of murine MSC was also exerted on antigen-specific responses [42]. Suppression of T cell proliferation did not require MHC restriction, but could also be mediated by allogeneic MSC [42,43].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

“…Krampera et al further demonstrated that the anti-proliferative activity of murine MSC was also exerted on antigen-specific responses [42]. Suppression of T cell proliferation did not require MHC restriction, but could also be mediated by allogeneic MSC [42,43]. Results confirming the in vivo immunosuppressive properties of MSC have been reported by Djouad et al, who demonstrated that growth of an allogeneic melanoma was significantly enhanced when the latter cells were co-transplanted together with the murine C3H10T1/2 MSC line [44].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

“…In addition, suppression of T cell proliferation induced by human MSC appears to depend, at least in part, on the cross-talk between the two cell populations, leading to the production of inflammatory cytokines such as IFN-c [39] and IL-1b [37] by activated immune cells. Inhibition of T cell proliferation resulted in the decreased production of effector Th1 cytokines [16,42,46]; however, the expression of activation markers in T cells that have been cultured with MSC remains a controversial issue [39,43,45,47]. Inhibition of T cell proliferation by MSC appears to be subsequent both to cell-to-cell interaction and to the release of soluble factors, and it is conceivable that discrepant findings reported in the literature reflect differences in the experimental conditions used [13,14,16,48,49].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

“…However, data confirming the generation of T reg cells upon MSC transplantation are still missing [16,42].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

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Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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Section: Msc and T Lymphocytesmentioning

confidence: 99%

Section: Msc and T Lymphocytesmentioning

confidence: 99%

Section: Msc and T Lymphocytesmentioning

confidence: 99%

“…However, data confirming the generation of T reg cells upon MSC transplantation are still missing [16,42].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

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Immunoregulatory function of mesenchymal stem cells

2006

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“…MSCs have also recently been demonstrated to suppress several T lymphocyte activities [6] and have been proposed as a possible treatment for acute graft-versus-host disease in humans [7]. Although the mechanisms mediating such effects are only partially understood, it is likely that both cell-to-cell contact and soluble factors are involved [8].…”

Section: Introductionmentioning

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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Neuroprotection and Immunomodulation With Mesenchymal Stem Cells in Chronic Experimental Autoimmune Encephalomyelitis

Kassis¹,

Grigoriadis²,

et al. 2008

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To investigate the therapeutic potential of mesenchymal stromal cells (MSCs) in the chronic model of experimental autoimmune encephalomyelitis (EAE). Design: Mesenchymal stromal cells were obtained from the bone marrow of naïve C57BL and green fluorescent protein-transgenic mice and cultured with Eagle minimum essential medium/alpha medium after removal of adhering cells. Following 2 to 3 passages, MSCs were injected intraventricularly or intravenously into mice in which chronic EAE had been induced with myelin oligodendrocyte glycoprotein 35-55 peptide. Results: In 8 separate experiments, the intravenously and intraventricularly injected green fluorescent proteinpositive MSCs were attracted to the areas of central nervous system inflammation and expressed galactocerebroside, O4, glial fibrillary acidic protein, and ␤-tubulin type III. The clinical course of chronic EAE was ameliorated in MSC-treated animals (0% mortality; mean [SE] maximal EAE score, 1.76 [1.01] and 1.8 [0.46] in the intraventricular and intravenous groups, respectively, vs 13% and 21% mortality and 2.80 [0.79] and 3.42 [0.54]

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Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide

Cited by 1,462 publications

References 34 publications

Immunoregulatory function of mesenchymal stem cells

Immunoregulatory function of mesenchymal stem cells

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

Neuroprotection and Immunomodulation With Mesenchymal Stem Cells in Chronic Experimental Autoimmune Encephalomyelitis

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