Search results for "Regulatory"
showing 10 items of 740 documents
CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease
2012
Background Based on their potency to control allergic diseases, regulatory T (Treg) cells represent a promising target for novel strategies to interfere with allergic airway inflammation. We have previously demonstrated that stimulation of the CD4 molecule on human Treg cells activates their suppressive activity in vitro and in vivo . Objective We sought to determine the effect of CD4-mediated Treg-cell activation on pulmonary inflammation in a humanized mouse model of allergic airway inflammation. Methods PBMCs obtained from donors allergic to birch pollen or from healthy donors were injected into NOD-severe combined immunodeficiency γc −/− mice, followed by allergen airway challenges and …
Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
2012
OBJECTIVE: From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. METHODS: Patients with active RA for whom TCZ had been prescribed by a rheumatologist were en…
Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in chronic Lyme borreliosis.
2013
The NapA protein of B. burgdorferi is essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-β and IL-10 by microglia cells. Collect…
Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus
1984
Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset less than 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 +/- 8.5% versus 70.7 +/- 8.0%), helper/inducer cells (OKT4+: 33.8 +/- 7.0% versus 47.1 +/- 8.3%), suppressor/cytotoxic cells (OKT8+: 18.5 +/- 7.3% versus 32 +/- 6.8%) and monocytes (OKM1+: 11.5 +/- 3.8% versus 19.9 +/- 5.2%) (p less than 0.…
Biomarker profile predicts clinical efficacy of extracorporeal photopheresis in steroid‐resistant acute and chronic graft‐vs‐host disease after allog…
2021
We conducted a multicenter interventional study to assess the efficacy of Therakos ECP to treat steroid-resistant graft-vs-host disease (SRes-GVHD) after allogeneic HSCT and to identify biomarkers of GVHD response. A total of 62 patients were treated for acute SRes-GVHD (n = 37) or chronic SRes-GVHD (n = 25). Median time to best response was 35 days (range, 28-85) and 90 days (range, 27-240) in acute and chronic SRes-GVHD, respectively. Overall, 27 patients (72.9%) with SRes-aGVHD responded to treatment (40.5% CR and 32.4% PR). The response rate was significantly higher in grade I-II than in grade III-IV aGVHD (100% vs 50.0%, respectively, P-value = .001). In chronic SRes-GVHD, 22 patients …
Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fast…
2008
Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C→T, APOA5 −1131T→C, and APOA5 56C→G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies…
The in vitro addition of methotrexate and/or methylprednisolone determines peripheral reduction in Th17 and expansion of conventional Treg and of IL-…
2014
The aim of our study was to evaluate methotrexate (MTX) and methylprednisolone (MP) effect on peripheral Th17 and Treg subsets in patients with rheumatoid arthritis (RA). We enrolled 15 patients (10 early RA and 5 long-standing disease) with active RA and 10 age-matched healthy donors as controls. Frequencies of Th17 and Treg were quantified using flow cytometry before and after in vitro addition of MTX, MP or both drugs. Our results showed a reduction in the overall Th17 population followed by an increase in Th17 IL-10+ and Treg, after in vitro treatment of PBMCs with the drugs in patients with early RA. Long-standing disease patients showed a less evident increase in Treg cells and less e…
SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease
2003
P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPL…
Immunologic effects of rituximab on the human spleen in immune thrombocytopenia
2011
Abstract Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell de…
The influence of bone marrow- and synovium-derived mesenchymal stromal cells from osteoarthritis patients on regulatory T cells in co-culture
2013
Summary There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs) in an allogeneic co-culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co-cultured with lymphocytes enriched in CD4+CD25+CD127– regulatory T cells (Treg+LC) from healthy donors. Treg proportions and MSC markers were assessed by fl…