Immunosuppressive therapy (IST) is administered to patients with acquired hemophilia A (AHA) to eradicate autoantibodies against coagulation factor VIII (FVIII). Data from registries previously demonstrated that IST is often complicated by adverse events, in particular infections. This pilot study was set out to assess the feasibility of reduced-intensity, risk factor-stratified IST.
View Article and Find Full Text PDFThe chemokine receptor CCR7 and its ligands CCL19 and CCL21 guide the homing and positioning of dendritic and T cells in lymphoid organs, thereby contributing to several aspects of adaptive immunity and immune tolerance. In the present study, we investigated the role of CCR7 in the pathogenesis of collagen-induced arthritis (CIA). By using a novel anti-human CCR7 antibody and humanized CCR7 mice, we evaluated CCR7 as a target in this autoimmune model of rheumatoid arthritis (RA).
View Article and Find Full Text PDFThe chemokine receptor CXCR5 is primarily expressed on B cells and Tfh cells and facilitates their migration towards B cell follicles. In the present study we investigated the role of the CXCL13/CXCR5 axis in the pathogenesis of rheumatoid arthritis (RA) and specifically addressed the impact of CXCR5-mediated T and B cell migration in this disease. Employing collagen-induced arthritis (CIA) we identify CXCR5 as an absolutely essential factor for the induction of inflammatory autoimmune arthritis.
View Article and Find Full Text PDFThe continuous migration of immune cells between lymphoid and nonlymphoid organs is a key feature of the immune system, facilitating the distribution of effector cells within nearly all compartments of the body. Furthermore, reaching their correct position within primary, secondary, or tertiary lymphoid organs is a prerequisite to ensure immune cells' unimpaired differentiation, maturation, and selection, as well as their activation or functional silencing. The superfamilies of chemokines and chemokine receptors are of major importance in guiding immune cells to and within lymphoid and nonlymphoid tissues.
View Article and Find Full Text PDFHoming of allogeneic donor T cells to recipient tissue is imperative for the development of acute graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this study we show that alteration of T cell homing due to integrin-β7 deficiency on T cells or its ligand MAdCAM-1 in BMT recipients contributes to the pathophysiology of experimental GVHD. In contrast, lack of CC chemokine receptor 9 on donor T cells alters tissue homing but does not impact GVHD survival.
View Article and Find Full Text PDFEctopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT.
View Article and Find Full Text PDFCCR7 is a homeostatically expressed chemokine receptor that is known to regulate the homing of various types of immune cells to primary, secondary, and tertiary lymphoid organs. Recent evidence suggests that, in addition to controlling cell migration, CCR7-mediated signals affect T-cell homeostasis in lymph nodes at various levels and also influence T-cell activation and polarization. In this review, we highlight these findings and discuss recently proposed functions of the CCR7 pathway in the induction and maintenance of chronic inflammation.
View Article and Find Full Text PDFThe chemokine receptor CCR7 has a central role in regulating homing and positioning of T cells and DCs to lymph nodes (LNs) and participates in T-cell development and activation. In this study, we addressed the role of CCR7 signaling in T(H) 2 polarization and B-cell activation. We provide evidence that the lack of CCR7 drives the capacity of naïve CD4(+) T cells to polarize toward T(H) 2 cells.
View Article and Find Full Text PDFLittle is known about the molecular mechanisms that determine the entry into the lymph node and intranodal positioning of lymph-derived cells. By injecting cells directly into afferent lymph vessels of popliteal lymph nodes, we demonstrate that lymph-derived T cells entered lymph-node parenchyma mainly from peripheral medullary sinuses, whereas dendritic cells (DCs) transmigrated through the floor of the subcapsular sinus on the afferent side. Transmigrating DCs induced local changes that allowed the concomitant entry of T cells at these sites.
View Article and Find Full Text PDFBackground: Lyme neuroborreliosis (LNB) is the second most common manifestation of Borrelia burgdorferi sensu lato (s. l.) infection in Europe.
View Article and Find Full Text PDFBackground: The purpose of this study was to compare technical and scale efficiency of primary care centers from the two largest Greek providers, the National Health System (NHS) and the Social Security Foundation (IKA) and to determine if, and how, efficiency is affected by various exogenous factors such as catchment population and location.
Methods: The sample comprised of 194 units (103 NHS and 91 IKA). Efficiency was measured with Data Envelopment Analysis (DEA) using three inputs, -medical staff, nursing/paramedical staff, administrative/other staff- and two outputs, which were the aggregated numbers of scheduled/emergency patient visits and imaging/laboratory diagnostic tests.