0000000000041464
AUTHOR
A Uhrig
IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules.
SUMMARYOur study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-γ) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 …
Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.
Abstract BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen- presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costi…
Chemokines: reliable markers for diagnosis of rejection and inflammation following orthotopic liver transplantation.
Ischemic Type Biliary Lesions nach orthotoper Lebertransplantation - ein immunologisches Problem?
Ischemic type biliary lesions (ITBL) are a major complication following orthotopic liver transplantation (OLT). In many cases re-OLT is indicated. Multiple factors have been claimed to be reasonable for ITBL; here we present a new immunological risk factor: CC-Chemokines play a key role in the recruitment of leukocytes during ischemia-reperfusion damage and acute rejection. Therefore the CC-chemokine-receptor 5 (CCR5) and its functionless CCR5-delta-32-polymorphism (CCR5Δ32) might have an influence on the grafts pathology after OLT. In 146 patients after OLT the CCR5 was analyzed with regard to the CCR5Δ32 by PCR. 120 patients (82,1%) showed a normal receptor (wildtype) whereas 26 patients …
Interleukin-10 expression is autoregulated at the transcriptional level in human and murine kupffer cells
Interleukin 10 (IL-10) is known to downregulate immune responses. The regulation of IL-10 gene expression therefore determines the outcome of local immune reactions. We investigated time course and downregulation of IL-10 production in primary Kupffer's cells (KC), which are known to secrete IL-10 in response to endotoxin challenge. Human and murine KC were isolated by centrifugal elutriation and investigated for IL-10 gene expression by a two-step amplification procedure (reverse transcriptase-polymerase chain reaction [PCR] followed by T7-polymerase chain reaction). We show that IL-10 messenger ribonucleic acid (mRNA) showed a >450 fold increase in KC 2 hours after endotoxin challenge. IL…
CC chemokine receptor 5Δ32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation
Ischemic-type biliary lesions are a major complication following orthotopic liver transplantation. They occur in up to 26% of liver transplant recipients. Among other factors, unknown immunologic factors have always been assumed to be partly responsible for these lesions. CC-chemokines and their receptors play a key role in postoperative immunomodulation after liver transplantation. The non-function CC-chemokine receptor 5Δ32 polymorphism (CCR5Δ32) has been shown to lead to a lower rate of acute rejection after kidney transplantation; in liver transplantation the role of CCR5Δ32 is unclear. We investigated the influence of the CCR5Δ32 after liver transplantation with special regard to ische…
Differenzielle Expression von CC-Chemokinen nach orthotoper Lebertransplantation während Rejektion und Infektion
Einleitung: Chemokine sind niedermolekulare Zytokine, die fur die Geweberekrutierung inflammatorischer Leukozyten verantwortlich sind. Eine Leukozyteninfiltration ist charakteristisch fur die akute Transplantatabstosung nach Lebertransplantation. Wir vermuten, dass die hepatische Chemokinsekretion als Vermittler von Abstosungsreaktionen nach Lebertransplantation eine Rolle spielen konnte. Daten zum Chemokinverlauf nach Lebertransplantation im peripheren Blut liegen bislang nicht vor. Material und Methoden: In dieser Untersuchung wurden die Serumchemokinkonzentrationen fur die CC-Chemokine CCL2 (Monocyte chemoattractant protein 1, MCP-1), CCL3 (Macrophage inflammatory protein I alpha, MIP-1γ…
The role of monocyte chemoattractant protein-1 in orthotopic liver transplantation.
Hepatic ischemia reperfusion injury as well as acute graft rejection (RE) after orthotopic liver transplantation (OLT) are associated with leukocyte invasion of the graft. Local synthesis of chemokines is a key reaction in the recruitment and activation of inflammatory leukocytes and consequent liver damage. In this paper we describe the role of monocyte chemoattractant protein (MCP)-1 (CCL2) in human OLT. We investigated the serum CC-chemokine levels for MCP-1 by specific ELISAs after OLT in 105 human liver allografts between September 1997 and January 2001. One hour after reperfusion we saw a significant (t test) increase of MCP-1 in peripheral blood (92.5 +/- 85.8 pg/mL to 774.2 +/- 319.…