scholarly journals Fc Gamma Receptors and Their Role in Antigen Uptake, Presentation, and T Cell Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Fabian Junker ◽  
John Gordon ◽  
Omar Qureshi
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Fc Gamma Receptors ◽  
Antigen Uptake

scholarly journals Activation Outcomes Induced in Naïve CD8 T-Cells by Macrophages Primed via “Phagocytic” and Nonphagocytic Pathways

2008 ◽  
Vol 19 (2) ◽  
pp. 701-710 ◽  
Author(s):  
Isabel María Olazabal ◽  
Noa Beatriz Martín-Cofreces ◽  
María Mittelbrunn ◽  
Gloria Martínez del Hoyo ◽  
Balbino Alarcón ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
Microtubule Organizing Center ◽  
Antigen Uptake ◽  
Soluble Peptide

The array of phagocytic receptors expressed by macrophages make them very efficient at pathogen clearance, and the phagocytic process links innate with adaptive immunity. Primary macrophages modulate antigen cross-presentation and T-cell activation. We assessed ex vivo the putative role of different phagocytic receptors in immune synapse formation with CD8 naïve T-cells from OT-I transgenic mice and compared this with the administration of antigen as a soluble peptide. Macrophages that have phagocytosed antigen induce T-cell microtubule-organizing center and F-actin cytoskeleton relocalization to the contact site, as well as the recruitment of proximal T-cell receptor signals such as activated Vav1 and PKCθ. At the same doses of loaded antigen (1 μM), “phagocytic” macrophages were more efficient than peptide-antigen–loaded macrophages at forming productive immune synapses with T-cells, as indicated by active T-cell TCR/CD3 conformation, LAT phosphorylation, IL-2 production, and T-cell proliferation. Similar T-cell proliferation efficiency was obtained when low doses of soluble peptide (3–30 nM) were loaded on macrophages. These results suggest that the pathway used for antigen uptake may modulate the antigen density presented on MHC-I, resulting in different signals induced in naïve CD8 T-cells, leading either to CD8 T-cell activation or anergy.

The Effects of Imatinib on the Function of Monocyte Derived Dendritic Cells Are Mediated Via the Inhibition of Akt and NF-kappaB Signal Transduction Pathways.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3453-3453
Author(s):  
Anette Rupf ◽  
Silke Appel ◽  
Markus M. Weck ◽  
Frank Grünebach ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Activation ◽  
Cell Activation ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Human Monocyte ◽  
Pi3 Kinase ◽  
Imatinib Treatment ◽  
Antigen Uptake

Abstract Imatinib is a novel tyrosine kinase inhibitor effective against Abl kinases, c-Kit and platelet-derived growth-factor receptor (PDGF-R) and is currently used for the treatment of patients with CML and GIST. However, little is known about the effects of imatinib on function and differentiation of non-transformed normal cells. Using this compound, we show that human monocyte derived DC generated in the presence of therapeutic concentrations of imatinib show a concentration dependent reduced expression of CD1a, HLA and co-stimulatory molecules as well as decreased activation-induced secretion of chemokines and cytokines involved in T cell activation. Moreover, exposure to imatinib reduces the capacity of DC to prime T cell responses that cannot be restored by the addition of IL-12 and which is not due to induction of apoptosis or IL-10 secretion. Using Western blot analyses we found that these effects are mediated by a pronounced downregulation of nuclear localized protein levels of NF-kB family members RelB, RelA and NF-kB p50. Furthermore, imatinib treatment inhibited the phosphorylation of Akt, indicating the involvement of the PI3 kinase pathways while not affecting the phosphorylation state of p38 and ERK1 MAP kinase. In line with these results, incubation of monocytes with PI3 kinase inhibitors resulted in a similar phenotype of DC as described above. Gene expression profiling utilizing DNA microarrays revealed upregulation of lysosomal genes and molecules preferentially expressed in monocytes/macrophages. However, in contrast to these observations, imatinib treatment had no effect on the incorporation of latex beads by DC and resulted in a reduced FITC-labeled dextran uptake. Importantly, utilizing blocking antibodies and tyrosine kinase inhibitors we demonstrate that the inhibitory effects of imatinib on DC differentiation are not mediated by PDGF-R and c-Kit but most likely via c-Abl tyrosine kinase. These results demonstrate that imatinib affects the antigen presenting function of DC on several levels: their phenotype, antigen uptake and processing as well as production of cytokines and chemokines.

Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation

Science ◽  
2007 ◽  
Vol 316 (5824) ◽  
pp. 612-616 ◽  
Author(s):  
S. Burgdorf ◽  
A. Kautz ◽  
V. Bohnert ◽  
P. A. Knolle ◽  
C. Kurts
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Antigen Uptake

scholarly journals Novel APC-like properties of human NK cells directly regulate T cell activation

2015 ◽  
Author(s):  
Jacob Hanna ◽  
Ofer Mandelboim
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
Antigen Uptake

Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane-enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell-mediated cytotoxicity and specific ligand recognition by cell surface-activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell-activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2–deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell-activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.

Interleukin-21 inhibits dendritic cell activation and maturation

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4090-4098 ◽  
Author(s):  
Katja Brandt ◽  
Silvia Bulfone-Paus ◽  
Donald C. Foster ◽  
René Rückert
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Contact Hypersensitivity ◽  
Dendritic Cell Activation ◽  
Antigen Uptake ◽  
Interleukin 21 ◽  
Mediated Contact

Abstract Interleukin 21 (IL-21) is a newly described cytokine with homology to IL-4 and IL-15. They belong to a cytokine family that uses the common γ chain for signaling but also have their private high-affinity receptors. Since it is well known that IL-4 modulates differentiation and activation of dendritic cells (DCs), we analyzed effects of IL-21 compared with IL-15 on DC differentiation, maturation, and function. Here we show that DCs generated with granulocyte-macrophage colony-stimulating factor (GMCSF) in the presence of IL-21 (IL-21DCs) differentiated into phenotypically and functionally altered DCs characterized by reduced major histocompatibility complex class II (MHCII) expression, high antigen uptake, and low stimulatory capacity for T-cell activation in vitro. Additionally, IL-21DCs completely failed to induce antigen (Ag)-specific T-cell mediated contact hypersensitivity. Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10. In contrast, when supplementing GMCSF with IL-15, DCs differentiated into mature antigen-presenting cells (APCs) with low antigen uptake and highly significant increased capacities to stimulate T cells in vitro and in vivo. Taken together, these results identify a dichotomous action of these structurally related cytokines on DCs, establishing IL-21 as inhibitory cytokine on DC activation and IL-15 as potent stimulator of DC function, making both cytokines interesting targets for therapeutic manipulation of DC-induced immune reactions. (Blood. 2003;102: 4090-4098)

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