Large extracellular vesicles derived from human regulatory macrophages (L-EVMreg) attenuate CD3/CD28-induced T-cell activation in vitro

Macrophages belong to the innate immune system, and we have recently shown that in vitro differentiated human regulatory macrophages (Mreg) release large extracellular vesicles (L-EV Mreg ) with an average size of 7.5 μm which regulate wound healing and angiogenesis in vitro. The aim of this study w...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2023-11, Vol.101 (11), p.1437-1448
Main Authors: Albrecht, Martin, Hummitzsch, Lars, Rusch, Rene, Eimer, Christine, Rusch, Melanie, Heß, Katharina, Steinfath, Markus, Cremer, Jochen, Fändrich, Fred, Berndt, Rouven, Zitta, Karina
Format: Article
Language:English
Subjects:
Angiogenesis
Biomedical and Life Sciences
Biomedicine
CD28 antigen
CD28 Antigens
CD3 antigen
CD4 antigen
CD4-Positive T-Lymphocytes
CD8 antigen
CD8-Positive T-Lymphocytes
Cell activation
Cell culture
Cell differentiation
Cell size
Centrifugation
Extracellular vesicles
Flow cytometry
Fluorescence microscopy
Granzyme B
Granzymes - pharmacology
Human Genetics
Humans
Immune system
Innate immunity
Internal Medicine
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Macrophages
Molecular Medicine
Monocytes
Original Article
Phosphatidylserine
Phosphatidylserines - pharmacology
Wound healing
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Summary:Macrophages belong to the innate immune system, and we have recently shown that in vitro differentiated human regulatory macrophages (Mreg) release large extracellular vesicles (L-EV Mreg ) with an average size of 7.5 μm which regulate wound healing and angiogenesis in vitro. The aim of this study was to investigate whether L-EV Mreg also affect the CD3/CD28-mediated activation of T-cells. Mreg were differentiated using blood monocytes and L-EV Mreg were isolated from culture supernatants by differential centrifugation. Activation of human T-cells was induced by CD3/CD28-coated beads in the absence or presence of Mreg or different concentrations of L-EV Mreg . Inhibition of T-cell activation was quantified by flow cytometry and antibodies directed against the T-cell marker granzyme B. Phosphatidylserine (PS) exposure on the surface of Mreg and L-EV Mreg was analyzed by fluorescence microscopy. Incubation of human lymphocytes with CD3/CD28 beads resulted in an increase of cell size, cell granularity, and number of granzyme B–positive cells ( P  
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-023-02374-9