The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells

Kirchberger, Stefanie; Majdic, Otto; Blüml, Stephan; Schrauf, Catharina; Leitner, Judith; Gerner, Christopher; Paster, Wolfgang; Gundacker, Nina; Sibilia, Maria; Stöckl, Johannes

doi:10.1182/blood-2008-02-138131

Cited by 12 publications

(23 citation statements)

References 62 publications

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“…For immunoprecipitation mAb p35 or mAb VIAP (isotype control) was loaded onto 7 Â 10 7 sheep anti-mouse IgG coupled Dynabeads (Dynal, Oslo, Norway) with 2.8 mm diameter as described in detail elsewhere [35,36]. After washing twice with PBS, the beads were incubated with cell culture SN for 12 h at 41C on a rotator.…”

Section: Immunoprecipitation Cytokine Depletion and Western Blottingmentioning

confidence: 99%

Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC

et al. 2010

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IL-35 is a heterodimer of EBV-induced gene 3 and of the p35 subunit of IL-12, and recently identified as an inhibitory cytokine produced by natural Treg in mice, but not in humans.Here we demonstrate that DC activated by human rhinoviruses (R-DC) induce IL-35 production and release, as well as a suppressor function in CD4 1 and CD8 1 T cells derived from human peripheral blood but not in naïve T cells from cord blood. The induction of IL-35-producing T cells by R-DC was FOXP3-independent, but blocking of B7-H1 (CD274) and sialoadhesin (CD169) on R-DC with mAb against both receptors prevented the induction of IL-35. Thus, the combinatorial signal delivered by R-DC to T cells via B7-H1 and sialoadhesin is crucial for the induction of human IL-35 1 Treg. These results demonstrate a novel pathway and its components for the induction of immune-inhibitory T cells.

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Section: Immunoprecipitation Cytokine Depletion and Western Blottingmentioning

confidence: 99%

Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC

et al. 2010

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“…PTPRC functions as a regulator of cytokine receptor signaling and influences cellular processes such as cell proliferation [78]. Upon activation of monocytes, proteolytic processing of PTPRC results in a protein fragment, which is released and acts as an inhibitor of T-cell proliferation [79]. The microRNA gene MIRN21 was expressed at higher levels after two months compared to pre-treatment levels.…”

Section: Discussionmentioning

confidence: 99%

Glatiramer acetate treatment effects on gene expression in monocytes of multiple sclerosis patients

Thamilarasan

Hecker

Goertsches

et al. 2013

J Neuroinflammation

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BackgroundGlatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to investigate the effects of GA therapy on the gene expression of monocytes.MethodsMonocytes were isolated from the peripheral blood of eight RRMS patients. The blood was obtained longitudinally before the start of GA therapy as well as after one day, one week, one month and two months. Gene expression was measured at the mRNA level by microarrays.ResultsMore than 400 genes were identified as up-regulated or down-regulated in the course of therapy, and we analyzed their biological functions and regulatory interactions. Many of those genes are known to regulate lymphocyte activation and proliferation, but only a subset of genes was repeatedly differentially expressed at different time points during treatment.ConclusionsOverall, the observed gene regulatory effects of GA on monocytes were modest and not stable over time. However, our study revealed several genes that are worthy of investigation in future studies on the molecular mechanisms of GA therapy.

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“…CD45 cleavages release a fragment of the CD45 cytoplasmic tail (ct-CD45). Soluble ct-CD45 selectively binds to pre-activated T cells and inhibits T cell proliferation [56]. Given that GalXM is a fungal antigen [11], [12] it might be that soluble ct-CD45 is released, in the presence of GalXM, and this might contribute to the inhibition of T cell activation.…”

Section: Discussionmentioning

confidence: 99%

Role of CD45 Signaling Pathway in Galactoxylomannan-Induced T Cell Damage

et al. 2010

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Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45−/− cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45−/− cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis.

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The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells

Cited by 12 publications

References 62 publications

Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC

Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC

Glatiramer acetate treatment effects on gene expression in monocytes of multiple sclerosis patients

Role of CD45 Signaling Pathway in Galactoxylomannan-Induced T Cell Damage

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