scholarly journals Cord-Blood-Derived Mesenchymal Stromal Cells Downmodulate CD4+ T-Cell Activation by Inducing IL-10-Producing Th1 Cells

2013 ◽  
Vol 22 (7) ◽  
pp. 1063-1075 ◽  
Author(s):  
Silvia Selleri ◽  
Mame Massar Dieng ◽  
Simon Nicoletti ◽  
Isabelle Louis ◽  
Christian Beausejour ◽  
...  
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Th1 Cells

scholarly journals Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yury Rubtsov ◽  
Кirill Goryunov ◽  
Аndrey Romanov ◽  
Yulia Suzdaltseva ◽  
George Sharonov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Mixed Cultures ◽  
Activated T Cells

Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rαthat negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration.

scholarly journals CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells

2003 ◽  
Vol 33 (3) ◽  
pp. 579-587 ◽  
Author(s):  
Kajsa Wing ◽  
Susanne Lindgren ◽  
Gittan Kollberg ◽  
Anna Lundgren ◽  
Robert A. Harris ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Activation ◽  
Cell Activation ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Cd4 T Cell

scholarly journals Thymoproteasome-Expressing Mesenchymal Stromal Cells Confer Protective Anti-Tumor Immunity via Cross-Priming of Endogenous Dendritic Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Jean-Pierre Bikorimana ◽  
Nehme El-Hachem ◽  
Abed El-Hakim El-Kadiry ◽  
Jamilah Abusarah ◽  
Natasha Salame ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
De Novo ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Phagocytic Cells ◽  
Cell Immunity

Proteasomes are complex macromolecular structures existing in various forms to regulate a myriad of cellular processes. Besides degrading unwanted or misfolded proteins (proteostasis), distinct immune functions were ascribed for the immunoproteasome and thymoproteasome (TPr) complexes. For instance, antigen degradation during ongoing immune responses mainly relies on immunoproteasome activity, whereas intrathymic CD8 T-cell development requires peptide generation by the TPr complex. Despite these substantial differences, the functional contribution of the TPr to peripheral T-cell immunity remains ill-defined. We herein explored whether the use of mesenchymal stromal cells (MSCs) engineered to exhibit altered proteasomal activity through de novo expression of the TPr complex can be exploited as a novel anti-cancer vaccine capable of triggering potent CD8 T-cell activation. Phenotypic and molecular characterization of MSC-TPr revealed a substantial decrease in MHCI (H2-Kb and H2-Dd) expression along with elevated secretion of various chemokines (CCL2, CCL9, CXCL1, LIX, and CX3CL1). In parallel, transcriptomic analysis pinpointed the limited ability of MSC-TPr to present endogenous antigens, which is consistent with their low expression levels of the peptide-loading proteins TAP, CALR, and PDAI3. Nevertheless, MSC-TPr cross-presented peptides derived from captured soluble proteins. When tested for their protective capacity, MSC-TPr triggered modest anti-tumoral responses despite efficient generation of effector memory CD4 and CD8 T cells. In contrast, clodronate administration prior to vaccination dramatically enhanced the MSC-TPr-induced anti-tumoral immunity clearly highlighting a refractory role mediated by phagocytic cells. Thus, our data elute to a DC cross-priming-dependant pathway in mediating the therapeutic effect of MSC-TPr.

scholarly journals Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner

2020 ◽  
Vol 21 (18) ◽  
pp. 6965 ◽  
Author(s):  
Tiago Carvalheiro ◽  
Carlos Rafael-Vidal ◽  
Beatriz Malvar-Fernandez ◽  
Ana P. Lopes ◽  
Jose M. Pego-Reigosa ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Neutralizing Antibody ◽  
Negative Regulator ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th17 Differentiation

Semaphorin (Sema)4A is a transmembrane glycoprotein that is elevated in several autoimmune diseases such as systemic sclerosis, rheumatoid arthritis and multiple sclerosis. Sema4A has a key role in the regulation of Thelper Th1 and Th2 differentiation and we recently demonstrated that CD4+ T cell activation induces the expression of Sema4A. However, the autocrine role of Sema4A on Th cell differentiation remains unknown. Naïve Th cells from healthy controls were cell sorted and differentiated into Th1, Th2 and Th17 in the presence or absence of a neutralizing antibody against the Sema4A receptor PlexinD1. Gene expression was determined by quantitative PCR and protein expression by ELISA and flow cytometry. We found that the expression of Sema4A is induced during Th1, Th2 and Th17 differentiation. PlexinD1 neutralization induced the differentiation of Th1 cells, while reduced the Th2 and Th17 skewing. These effects were associated with an upregulation of the transcription factor T-bet by Th1 cells, and to downregulation of GATA3 and RORγt in Th2 cells and Th17 cells, respectively. Finally, PlexinD1 neutralization regulates the systemic sclerosis patients serum-induced cytokine production by CD4+ T cells. Therefore, the autocrine Sema4A-PlexinD1 signaling acts as a negative regulator of Th1 skewing but is a key mediator on Th2 and Th17 differentiation, suggesting that dysregulation of this axis might be implicated in the pathogenesis of CD4+ T cell-mediated diseases.

scholarly journals Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation

Stem Cells ◽  
2015 ◽  
Vol 34 (2) ◽  
pp. 516-521 ◽  
Author(s):  
Martin Böttcher ◽  
Andreas D. Hofmann ◽  
Heiko Bruns ◽  
Martina Haibach ◽  
Romy Loschinski ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
Aerobic Glycolysis ◽  
Mtor Signaling

scholarly journals CD14 Expressing Precursors Give Rise to Highly Functional Conventional Dendritic Cells for Use as Dendritic Cell Vaccine

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3818
Author(s):  
Maud Plantinga ◽  
Denise A. M. H. van den Beemt ◽  
Ester Dünnebach ◽  
Stefan Nierkens
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Activated T Cells

Induction of long-lasting immunity by dendritic cells (DCs) makes them attractive candidates for anti-tumor vaccination. Although DC vaccinations are generally considered safe, clinical responses remain inconsistent in clinical trials. This initiated studies to identify subsets of DCs with superior capabilities to induce effective and memory anti-tumor responses. The use of primary DCs has been suggested to overcome the functional limitations of ex vivo monocyte-derived DCs (moDC). The ontogeny of primary DCs has recently been revised by the introduction of DC3, which phenotypically resembles conventional (c)DC2 as well as moDC. Previously, we developed a protocol to generate cDC2s from cord blood (CB)-derived stem cells via a CD115-expressing precursor. Here, we performed index sorting and single-cell RNA-sequencing to define the heterogeneity of in vitro developed DC precursors and identified CD14+CD115+ expressing cells that develop into CD1c++DCs and the remainder cells brought about CD123+DCs, as well as assessed their potency. The maturation status and T-cell activation potential were assessed using flow cytometry. CD123+DCs were specifically prone to take up antigens but only modestly activated T-cells. In contrast, CD1c++ are highly mature and specialized in both naïve as well as antigen-experienced T-cell activation. These findings show in vitro functional diversity between cord blood stem cell-derived CD123+DC and CD1c++DCs and may advance the efficiency of DC-based vaccines.

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