Suppression of T-Cell Proliferation by Normal Density Granulocytes Led to CD183 Downregulation and Cytokine Inhibition in T-Cells.

Normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from healthy donors preferentially inhibit T helper 1 (Th1) cells and investigated the myeloid-derived suppressive effect in different T-cell populations. We found that NDG-induced suppression of T-cell proliferation was contact dependent, mediated by integrin CD11b, and dependent on NDG-production of reactive oxygen species (ROS).

Methotrexate Treatment Suppresses Monocytes in Nonresponders to Pneumococcal Conjugate Vaccine in Rheumatoid Arthritis Patients.

Patients with rheumatoid arthritis (RA) have an increased risk of infections; therefore, immunization against vaccine-preventable diseases is important. Methotrexate (MTX) impairs the antibody response to pneumococcal conjugate vaccine (PCV) in patients with arthritis, and the underlying mechanism is largely unknown. Here, we investigate the potential role of the innate immune system in the faltering antibody response following PCV vaccination in RA patients treated with MTX.

Bone Marrow Neutrophils of Multiple Myeloma Patients Exhibit Myeloid-Derived Suppressor Cell Activity.

Activated normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from blood and bone marrow of multiple myeloma (MM) patients have the ability to suppress T-cells, as MDSC. MM is an incurable plasma cell malignancy of the bone marrow.

Increased Frequencies of Switched Memory B Cells and Plasmablasts in Peripheral Blood from Patients with ANCA-Associated Vasculitis.

B cells are thought to play a central role in the pathogenesis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). ANCAs have been proposed to cause vasculitis by activating primed neutrophils to damage small blood vessels. We studied a cohort of AAV patients of which a majority were in remission and diagnosed with granulomatosis with polyangiitis (GPA).

Eosinophils in anti-neutrophil cytoplasmic antibody associated vasculitis.

Background: Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) are characterized by autoimmune small vessel inflammation. Eosinophils are multifunctional cells with both pro-inflammatory and immunoregulatory properties. Tissue activated eosinophils secrete cyto- and chemokines and form extracellular traps (EETs), they release free granules and produce reactive oxygen species.

Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus.

Introduction: Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE.

Secretory lysosome targeting and induced secretion of human soluble TNF-alpha receptor in murine hematopoietic cells in vivo as a principle for immunoregulation in inflammation and malignancy.

Objective: Systemic administration of immunotherapeutics often gives rise to severe side effects. A local deposition, using secretory lysosomes of hematopoietic cells as vehicles for delivery, can overcome this problem. In the present study, the validity of this concept was investigated using retroviral transduction of the human soluble tumor necrosis factor-alpha receptor 1 (hsTNFR1) into murine bone marrow cells, followed by transfer of the genetically modified cells into irradiated mice.

Backcross and partial advanced intercross analysis of nonobese diabetic gene-mediated effects on collagen-induced arthritis reveals an interactive effect by two major loci.

Genetic segregation analysis between NOD and C57BL strains have been used to identify loci associated with autoimmune disease. Only two loci (Cia2 and Cia9) had earlier been found to control development of arthritis, whereas none of the previously identified diabetes loci was of significance for arthritis. We have now made a high-powered analysis of a backcross of NOD genes on to the B10.

Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice.

Relapsing polychondritis (RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4+ patients are more commonly affected than controls.

A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels.

The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow.

The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross.

The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis.