Showing 1 - 4 of 4 results for "10970"
- ReferenceA. H. Mandarano et al. (dec 2019) The Journal of clinical investigation
Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and post-exertional malaise. There is little known about the metabolism of specific immune cells in ME/CFS patients. To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 ME/CFS patients and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism, and plasma cytokines. We found that ME/CFS CD8+ T cells have reduced mitochondrial membrane potential compared to healthy controls. Both CD4+ and CD8+ T cells from ME/CFS patients had reduced glycolysis at rest, while CD8+ T cells also had reduced glycolysis following activation. ME/CFS patients had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from healthy control subjects. Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease. View PublicationCatalog #: Product Name: 10970 ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator 17853 EasySep™ Human CD8 Positive Selection Kit II 17854 EasySep™ Human CD19 Positive Selection Kit II 17855 EasySep™ Human CD56 Positive Selection Kit II 17952 EasySep™ Human CD4+ T Cell Isolation Kit 85415 SepMate™-15 (IVD) Catalog #: 10970 Product Name: ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator Catalog #: 17853 Product Name: EasySep™ Human CD8 Positive Selection Kit II Catalog #: 17854 Product Name: EasySep™ Human CD19 Positive Selection Kit II Catalog #: 17855 Product Name: EasySep™ Human CD56 Positive Selection Kit II Catalog #: 17952 Product Name: EasySep™ Human CD4+ T Cell Isolation Kit Catalog #: 85415 Product Name: SepMate™-15 (IVD) - ReferenceR. Gao et al. (may 2020) Science advances 6 20 eaaz8411
Competition between PAF1 and MLL1/COMPASS confers the opposing function of LEDGF/p75 in HIV latency and proviral reactivation.
Transcriptional status determines the HIV replicative state in infected patients. However, the transcriptional mechanisms for proviral replication control remain unclear. In this study, we show that, apart from its function in HIV integration, LEDGF/p75 differentially regulates HIV transcription in latency and proviral reactivation. During latency, LEDGF/p75 suppresses proviral transcription via promoter-proximal pausing of RNA polymerase II (Pol II) by recruiting PAF1 complex to the provirus. Following latency reversal, MLL1 complex competitively displaces PAF1 from the provirus through casein kinase II (CKII)-dependent association with LEDGF/p75. Depleting or pharmacologically inhibiting CKII prevents PAF1 dissociation and abrogates the recruitment of both MLL1 and Super Elongation Complex (SEC) to the provirus, thereby impairing transcriptional reactivation for latency reversal. These findings, therefore, provide a mechanistic understanding of how LEDGF/p75 coordinates its distinct regulatory functions at different stages of the post-integrated HIV life cycles. Targeting these mechanisms may have a therapeutic potential to eradicate HIV infection. View PublicationCatalog #: Product Name: 10970 ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator 10971 ImmunoCult™ Human CD3/CD28 T Cell Activator 17852 EasySep™ Human CD4 Positive Selection Kit II 17952 EasySep™ Human CD4+ T Cell Isolation Kit Catalog #: 10970 Product Name: ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator Catalog #: 10971 Product Name: ImmunoCult™ Human CD3/CD28 T Cell Activator Catalog #: 17852 Product Name: EasySep™ Human CD4 Positive Selection Kit II Catalog #: 17952 Product Name: EasySep™ Human CD4+ T Cell Isolation Kit - ReferenceF. Muhammad et al. (nov 2019) Scientific reports 9 1 16941
PD-1+ melanocortin receptor dependent-Treg cells prevent autoimmune disease.
Experimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis marked by ocular autoantigen-specific regulatory immunity in the spleen. The melanocortin 5 receptor (MC5r) and adenosine 2 A receptor (A2Ar) are required for induction of post-EAU regulatory T cells (Tregs) which provide resistance to EAU. We show that blocking the PD-1/PD-L1 pathway prevented suppression of EAU by post-EAU Tregs. A2Ar induction of PD-1+FoxP3+ Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. Further, lower body mass index correlated with responsiveness to stimulation of this pathway. These observations indicate an importance of the PD-1/PD-L1 pathway to provide resistance to relapsing uveitis and shows a reduced capacity of uveitis patients to induce Tregs when stimulated through melanocortin receptors, but that it is possible to bypass this part of the pathway through direct stimulation of A2Ar. View PublicationCatalog #: Product Name: 10970 ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator 15021 RosetteSep™ Human T Cell Enrichment Cocktail Catalog #: 10970 Product Name: ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator Catalog #: 15021 Product Name: RosetteSep™ Human T Cell Enrichment Cocktail - ReferenceGrö et al. (JUL 2016) Blood
LFA-1 integrin antibodies inhibit leukocyte α4β1-mediated adhesion by intracellular signaling.
Binding of ICAM-1 (intercellular adhesion molecule-1) to the β2-integrin LFA-1 (leukocyte function associated antigen-1) is known to induce crosstalk to the α4β1 integrin. Using different LFA-1 monoclonal antibodies we have been able to study the requirement and mechanism of action for the crosstalk in considerable detail. LFA-1 activating antibodies and those inhibitory antibodies that signal to α4β1 induce phosphorylation of Thr-758 on the β2-chain, which is followed by binding of 14-3-3 proteins and signaling through the G protein exchange factor Tiam1. This results in dephosphorylation of Thr-788/789 on the β1-chain of α4β1 and loss of binding to its ligand VCAM-1 (vascular cell adhesion molecule-1). The results show that with LFA-1 antibodies, we can either 1) activate LFA-1 and inhibit α4β1, 2) inhibit both LFA-1 and α4β1, 3) inhibit LFA-1 but not α4β1 or 4) not affect LFA-1 or α4β1 These findings are important for the understanding of integrin regulation and for the interpretation of the effect of integrin antibodies and their use in clinical applications. View PublicationCatalog #: Product Name: 10970 ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator Catalog #: 10970 Product Name: ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator