Mesenchymal Stem Cells Inhibit the Expression of CD25 (Interleukin‐2 Receptor) and CD38 on Phytohaemagglutinin‐Activated Lymphocytes

Blanc, Katarina Le; Rasmusson, Ida; Götherström, Cecilia; Seidel, Catharina; Sundberg, Berit; Sundin, Mikael; Rosendahl, Kerstin; Tammik, Charlotte; Ringdén, Olle

doi:10.1111/j.0300-9475.2004.01483.x

Cited by 307 publications

(254 citation statements)

References 35 publications

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“…Allogenic MSCs from any passage did not elicit the upregulation of CD69 and CD25 on T cells, indicating that long-term culture did not impair the low immunogenicity of MSCs (data not shown); while MSCs significantly inhibited PHA-induced upregulation of CD69 and CD25, which is consistent with previous reports (21)(22)(23) no MSCs control), respectively, when MSCs from P7 were added to the co-culture. The addition of MSCs from P13 did not exert any suppressive influences on the expression of activation antigens on the PHA-stimulated T cells (for both CD25 and CD69, P>0.05 vs. no MSCs control; Fig.…”

Section: Effects Of Mscs In Long-term Culture On the Activation Of T supporting

confidence: 89%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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Abstract. Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA β-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).

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Section: Effects Of Mscs In Long-term Culture On the Activation Of T supporting

confidence: 89%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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“…Thus, further investigations will show whether other cytokines, or crosstalk with other signalling pathways (e.g. TLR signalling), could enhance the human MSC immunoregulatory response.It has been speculated that MSC-mediated T-cell immunosuppression may be due to modulation of CD25 and CD69 expression on T cells [24,30]. However, the data presented in this study show that neither the MSC-induced maintenance of CD69 expression, nor the reduction of normal levels of CD25, appears to be correlated with immunosuppression as judged by inhibition of T-cell proliferation.…”

contrasting

confidence: 75%

“…2D). As previously published, this lower expression of CD25 may be related to defective T-cell proliferation [24], although this phenomenon could not be rescued by higher concentrations of IL-2 (100 ng/mL, data not shown). T cells co-cultured with MSCs transduced with pLV-IKK-βi also maintained CD69 expression throughout the culture period despite the previously observed recovery of cellular proliferation ( Fig.…”

supporting

confidence: 55%

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

Dorronsoro¹,

Ferrin²,

Salcedo³

et al. 2013

Eur J Immunol

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Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune responses, little is known about the mechanisms that underpin these processes. In this study, we show that immunosupression is mediated by activation of nuclear factor kappa B (NF-κB) in human MSCs. This pathway is activated by TNF-α that is generated following TCR stimulation of T cells. Inhibition of NF-κB through silencing of IκB kinase β or the TNF-α receptor abolishes the immunosuppressive capacity of MSCs. Our data also indicate that MSC-associated NF-κB activation primarily leads to inhibition of T-cell proliferation with little effect on expression of the activation markers CD69 and CD25. Thus, our data support the hypothesis that the TNF-α/NF-κB signalling pathway is required for the initial priming of immunosuppressive function in human MSCs. Interestingly, drugs that interfere with NF-κB activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for immunosuppression regimens in the clinic. Keywords:Immunoregulation r MSC r NF-κB r TNF-α See accompanying Commentary by Pistoia and RaffaghelloAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMesenchymal stromal cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into multiple lineages. These cells are found in a variety of tissues during development, of which BM represents the most common source for research purposes. From a clinical perspective, MSCs are considered to Correspondence: Dr. César Trigueros e-mail: ctrigueros@inbiomed.org have a potential use in tissue repair for bone, cartilage and tendon. However, due to their immunomodulatory properties and their inclusion as a stromal component of the marrow microenvironment, MSCs are currently utilised in other therapeutic scenarios, such as those encountered in hematopoietic stem cell transplantation, GVH disease or chronic inflammatory diseases [1,2]. These characteristics, together with their low immunogenicity [1,2], have opened up promising new avenues of research for the use of MSCs not only in autologous but also in allogeneic settings.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 480-488 Immunomodulation 481 The immunomodulatory activity of MSCs, directed against a wide range of effector cells of both the innate and adaptive immune system, has been described. Communication between MSCs and immune cells, through cell-to-cell contact-dependent and/or contact-independent mechanisms, has been shown to lead to increased production of soluble immunomodulatory factors such as indoleamine 2,3-deoxigenase [3,4], prostaglandin E2 [5][6][7], iNOS [8], transforming growth factor β (TGF-β), hepatocyte growth factor [9], human lymphocytes Ag molecule 5 and IL-10 [10]. Thus, the picture is complex, as it is likely that multiple regulatory mechanisms exist without an obvious hierarchy of importance.The inflammatory e...

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“…The veto-like (forbidding) activity of MSCs (Potian et al, 2003;Tscherning and Claesson, 1993) inhibits T-cell proliferation (Bartholomew et al, 2002;Bocelli-Tyndall et al, 2007;Di Nicola et al, 2002;Klyushnenkova et al, 2005) via induction of T-cell quiescence upon blockade into G0/G1 (Glennie et al, 2005) and downregulation of the T-cell activation markers CD25, CD38, and CD69 (Groh et al, 2005;Le Blanc et al, 2004) and of IL-2 production (Park et al, 2011). MSCs also inhibit Th17 differentiation from both naïve and memory T cell precursors in vitro, as well as preventing the efflux of naturally occurring Th17 cells derived from inflammation sites in vivo (Duffy et al, 2011).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

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

Pluchino

Cossetti

2013

Glia

111

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 Inhibit the Expression of CD25 (Interleukin‐2 Receptor) and CD38 on Phytohaemagglutinin‐Activated Lymphocytes

Cited by 307 publications

References 35 publications

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

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

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