scholarly journals Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytes

2009 ◽  
Vol 39 (12) ◽  
pp. 3436-3446 ◽  
Author(s):  
Monique E. Quaedackers ◽  
Carla C. Baan ◽  
Willem Weimar ◽  
Martin J. Hoogduijn
Keyword(s):  
T Lymphocytes ◽  
Contact Interaction ◽  
Stromal Cells ◽  
Cell Contact ◽  
Adipose Derived Stromal Cells ◽  
Activated T Lymphocytes

Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact

1998 ◽  
Vol 63 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Siba P. Bhattacharyya ◽  
llana Drucker ◽  
Tamar Reshef ◽  
Arnold S. Kirshenbaum ◽  
Dean D. Metcalfe ◽  
...  
Keyword(s):  
Mast Cells ◽  
T Lymphocytes ◽  
Cytokine Production ◽  
Cell Contact ◽  
Human Mast Cells ◽  
Activated T Lymphocytes

HLA-G Transference From Multipotent Mesenchymal Stromal Cells to Activated T-Lymphocytes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3674-3674
Author(s):  
Rodrigo A Panepucci ◽  
Felipe Saldanha-Araujo ◽  
Kelen C R Malmegrim ◽  
Fabio M Oliveira ◽  
Patricia V B Palma ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Lymphocytes ◽  
Confocal Microscopy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nuclear Staining ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Membrane Bound

Abstract Abstract 3674 Poster Board III-610 HLA-G is a nonclassic human leukocyte antigen which is characterized by its limited variability, its highly tissue-specific expression and for its very distinct immunological role. Instead of triggering immune responses, HLA-G is exclusively inhibitory, suppressing immune cell functions. For instance, HLA-G is expressed by cells in sites considered immunologically privileged, such as the fetal cytotrophoblast, at the fetal–maternal interface, were it acts protecting the fetal tissue from the mother's immune response. HLA-G is also pathologically expressed in a diverse set of tumors, acting as an immunescape mechanism. Trough splicing mechanisms, HLA-G can be expressed as a membrane-bound or as a soluble isoform. Interestingly, the transference of membrane fragments between cells, a process called trogocytosis, can spread HLA-G inhibitory function beyond the reach of HLA-G-expressing cells. For instance, upon trogocytosis, effector CD4+ T cells stop proliferating, stop responding to stimulation, and behave as regulatory T cells. Recently, mesenchymal stromal cells (MSC) were shown to secrete soluble HLA-G, adding to the existing set of secreted molecules, by which MSC can modulate cells of the immune system. Despite the importance of secreted factors, cell-to-cell contacts have an important role in the immunological effects exerted by MSC. Based in these facts, we hypothesized that one of the mechanisms used by MSC to immunomodulate T cells, could involve trogocytosis mediated HLA-G transference. To test this, CD3+ T cell were immunomagnetically selected from peripheral blood mononuclear cells (PBMC) and pre-activated for 72hs using anti-CD2/CD3/CD28 beads. Activated T-cells were then incubated for 30 min, alone or with MSC. After this period, cells were recovered and the transfer of membrane bound molecules from MSC to T-cells was analyzed by flow cytometry (3 experiments) using antibodies against HLA-G. Confocal microscopy was carried in an additional experiment, using antibodies against HLA-G, CD140B (a specific MSC marker) and CD3. DAPI was used for nuclear staining. Flow cytometry analysis revealed that activated CD3+ T-cells did not express HLA-G, while MSC expressed HLA-G intracytoplasmatic. After 30 min of co-incubation, membrane bound HLA-G was detected in a variable percentage of CD3+ cells, ranging from 3 to up to 16%, characterizing the transfer of HLA-G from MSC to CD3+ T-cells. Confocal microscopy revealed that activated T-cells cultured alone did not stained for HLA-G or CD140B, while, about 12% of the CD3+ cells stained for membrane HLA-G, following the 30 min incubation with MSC. Additionally, CD140B was also transferred from MSC to CD3+ T-cells. These data are the first demonstration of trogocytosis mediated transfer of HLA-G from MSC to activated T lymphocytes. Given the significance of HLA-G expression and trogocytosis in normal and pathological situations, this newly described immunological mechanism should be considered in the development and application of MSC-based therapies. Supported by CNPq and FAPESP. Disclosures: No relevant conflicts of interest to declare.

Prostaglandin E2 Plays a Key Role in the Immunosuppressive Properties of Adipose Tissue-Derived Mesenchymal Stromal Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3636-3636
Author(s):  
Rosa Yañez ◽  
Alberto Oviedo ◽  
Montserrat Aldea ◽  
Antonio Rubio ◽  
Juan A. Bueren ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cytokine Secretion ◽  
Activated T Cells ◽  
Expression Of Genes ◽  
Activated T Lymphocytes

Abstract Abstract 3636 Poster Board III-572 Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells that can be obtained from several tissues. These cells have a limited immunogenicity, and their immunosuppressive properties have led to their use to treat graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cells transplantation. In previous studies, we demonstrated that adipocyte tissue-derived MSCs (Ad-MSCs) suppress activated T cells proliferation and prevent GVHD in a haploidentical hematopoietic transplantation mouse model (Yañez, Stem Cells 2006). In the present study, we have investigated the mechanisms participating in the immunosuppressive properties of human Ad-MSCs. First, we confirmed that the addition of Ad-MSCs to activated T lymphocytes inhibited the production of pro-inflammatory cytokines (TNF-a, IFN-g, IL-6 and IL-12), and increased the secretion of the immunosuppressive IL-10. In these co-cultures, high levels of PGE2 were detected. The addition of indomethacin (IDM), an inhibitor of PGE2, restored the proliferation of activated T lymphocytes and increased the expression of genes related with proliferation. Furthermore, an increase in the expression of genes related with transcription factors and cytokines involved in the TH1/TH2 differentiation pathway of the activated T cells was detected. These results show that PGE2 plays a key role in the immunosuppressive effects of Ad-MSCs over activated T lymphocytes. Although, strikingly, the blockade of PGE2 by IDM did not restore the pro-inflammatory cytokine secretion profile in the Ad-MSCs/activated T lymphocytes co-cultures, the increase in the expression of activation and differentiation-related genes suggests a restoration, at an early time, of the cytokine secretion of the activated T lymphocytes. Analyses at different time-points after the addition of IDM are being conducted to confirm this hypothesis. When TGF-b was determined in these cultures, no changes were detected by the addition of Ad-MSCs to activated T lymphocytes cultures, showing that this factor does not account for the inhibitory effects of Ad-MSCs over activated T cells. Next, we studied the impact of Ad-MSCs over the maturation of dendritic cells. We generated immature myeloid (m-DCs) and plasmocytoid (p-DCs) dendritic cells, and induced their maturation with LPS. We found that in co-culture with Ad-MSCs, dendritic cells remained in an immature state, shown by decreased CD83 and CD80 expression, and by a decreased secretion of TNF-β by myeloid-DCs (m-DCs), and an increased production of IL-10 by plasmocytoid-DCs (p-DCs). The blockade by IDM of the PGE2 present in the co-cultures resulted in the maturation of p-DCs, but not of m-DCs, that remained in an immature state. These results show that PGE2 accounts for the immunosuppressive effects of Ad-MSCs over the maturation of p-DCs, but not over the maturation of m-DCs. Finally, when TGF-b1 was studied, no changes in the very low values of TGF-b levels were detected in the supernatants of m-DCs and p-DCs co-cultured Ad-MSCs, showing that this factor does not play an important role in the effects of Ad-MSCs on the maturation of m-DCs and p-DCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells

1987 ◽  
Vol 132 (1) ◽  
pp. 43-57
Author(s):  
H. Wekerle ◽  
D. Sun ◽  
R. L. Oropeza-Wekerle ◽  
R. Meyermann
Keyword(s):  
T Cells ◽  
Nervous System ◽  
T Lymphocytes ◽  
Interferon Gamma ◽  
Glial Cells ◽  
T Lymphocyte ◽  
Cell Contact ◽  
Immune Reactivity ◽  
Antigen Specificity ◽  
Activated T Lymphocytes

The vertebrate central nervous system (CNS) has been traditionally thought to be inaccessible for the passenger lymphocytes of the immune system. This does not seem to be the case: activated T-lymphocytes can readily cross the endothelial blood-brain barrier (BBB) and some glial cells, notably the astrocytes, seem to be programmed to act as most efficient and complex partners for antigen-specific T-lymphocytes. We used myelin basic protein (MBP) specific permanent rat T-lymphocyte lines as probes to assess the immune status of the CNS. These cells, upon activation in vitro, are able to transfer lethal, experimentally induced autoimmune-encephalomyelitis (EAE) to normal syngeneic recipients. Activated T-lymphocytes, but not resting ones, can break through the BBB irrespective of their antigen specificity. Immune surveillance of the CNS thus seems to be executed by activated T-lymphocytes. Having crossed the BBB, the activated T-cells interact with local glial cells by releasing factors, including interferon-gamma, which induced astrocytes to synthesize and express, on their membranes, class II major histocompatibility antigens (Ia determinants), which are critically required for immunogenic presentation of antigens to T-cells. Indeed, Ia-induced astrocytes of the CNS (and the Schwann cells of peripheral nerves) are efficient antigen presenter cells, which are able strongly to up-regulate antigen-reactive T-lymphocytes. In addition, it has recently been shown that at least some astrocytes are able to down-regulate immune cells. Some, but not all, astrocytes are capable of suppressing activation of T-cells. This suppression can be modulated by interferon-gamma, and is sensitive to irradiation. The question of whether suppression is mediated by direct cell-to-cell contact or via soluble mediators (e.g. apolipoprotein E) is under investigation. Astrocytes have been found to be most subtle regulators of immuno-competent T-cells. Most probably they are centrally involved in physiological immune reactivity of the CNS, and it will be tempting to learn how far glial cells are involved in transmitting regulatory signals between the immune and nervous systems.

scholarly journals Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes

2011 ◽  
Vol 7 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Felipe Saldanha-Araujo ◽  
Flávia I.S. Ferreira ◽  
Patrícia V. Palma ◽  
Amélia G. Araujo ◽  
Regina H.C. Queiroz ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Activated T Lymphocytes

Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles

2017 ◽  
Vol 17 (11) ◽  
Author(s):  
Valentina Cocce ◽  
Luigi Balducci ◽  
Maria L. Falchetti ◽  
Luisa Pascucci ◽  
Emilio Ciusani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Stromal Cells ◽  
Adipose Derived Stromal Cells

scholarly journals Salidroside promoted osteogenic differentiation of adipose-derived stromal cells through Wnt/β-catenin signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiao-hua Li ◽  
Fu-ling Chen ◽  
Hong-lin Shen
Keyword(s):  
Western Blot ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Stromal Cells ◽  
Differentially Expressed ◽  
Calcium Deposition ◽  
Western Blot Assay ◽  
Adipose Derived Stromal Cells ◽  
Interfering Rna

Abstract Background Bone disease causes short-term or long-term physical pain and disability. It is necessary to explore new drug for bone-related disease. This study aimed to explore the role and mechanism of Salidroside in promoting osteogenic differentiation of adipose-derived stromal cells (ADSCs). Methods ADSCs were isolated and treated with different dose of Salidroside. Cell count kit-8 (CCK-8) assay was performed to assess the cell viability of ADSCs. Then, ALP and ARS staining were conducted to assess the early and late osteogenic capacity of ADSCs, respectively. Then, differentially expressed genes were obtained by R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially expressed genes were further analyzed. The expression of OCN, COL1A1, RUNX2, WNT3A, and β-catenin were measured by real-time PCR and Western blot analysis. Last, β-catenin was silenced by small interfering RNA. Results Salidroside significantly increased the ADSCs viability at a dose-response manner. Moreover, Salidroside enhanced osteogenic capacity of ADSCs, which are identified by enhanced ALP activity and calcium deposition. A total of 543 differentially expressed genes were identified between normal and Salidroside-treated ADSCs. Among these differentially expressed genes, 345 genes were upregulated and 198 genes were downregulated. Differentially expressed genes enriched in the Wnt/β-catenin signaling pathway. Western blot assay indicated that Salidroside enhanced the WNT3A and β-catenin expression. Silencing β-catenin partially reversed the promotion effects of Salidroside. PCR and Western blot results further confirmed these results. Conclusion Salidroside promoted osteogenic differentiation of ADSCs through Wnt/β-catenin signaling pathway.

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