Search results for "topoi"
showing 10 items of 701 documents
CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib–associated renal carcinoma antigens with ubiquitous or…
2004
AbstractAllogeneic hematopoietic stem cell transplantation can induce considerable tumor remissions in metastatic renal-cell carcinoma (RCC) patients. The precise effector mechanisms mediating these graft-versus-tumor reactions are unknown. We studied RCC-directed CD8+ T-cell responses in blood lymphocytes of healthy individuals matched with established RCC cell lines for HLA-class I. In 21 of 22 allogeneic mixed lymphocyte/tumor-cell cultures (MLTCs), RCC-reactive cytotoxic T-lymphocytes (CTLs) were readily obtained. From MLTCs, 121 CD8+ CTL clones with memory phenotype were isolated. Their anti–RCC reactivity was restricted by multiple classical HLA-Ia molecules, in particular by HLA-A2, …
Hematopoietic Growth Factors Are Differentially Regulated in Monocytes and CD4+T Lymphocytes: Influence of IFN-α and Interleukin-4
1998
We investigated the influence of interferon-alpha (IFN-alpha) on the synthesis of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by monocytes and activated T helper cells. IFN-alpha inhibited the production of GM-CSF in unstimulated and lipopolysaccharide (LPS)-activated monocytes to the same extent as was observed in the presence of IL-4. In highly purified CD4+ T cells, which were activated by incubation with immobilized anti-CD3 antibody and anti-CD28, IFN-alpha reduced production of GM-CSF to 47%. In contrast, GM-CSF production in activated T cells was unaffected by exogenously added IL-4. The production of IL-3 by T helper cells was significantly inh…
TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Acti…
2020
Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting…
Reconstitution of CD52-Negative CD4 T Cells after Alemtuzumab-Based T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation
2008
Abstract The human CD52 molecule is the target of the monoclonal antibody Alemtuzumab, which is used for treating patients with chemo-refractory chronic lymphocytic leukemia as well as for T cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). The molecule is expressed on the surface of lymphocytes, dendritic cells and to a lesser extent on blood-derived monocytes. Previously, investigators have demonstrated that the surface expression of CD52 on T cells is down-regulated after in vitro incubation with Alemtuzumab. By treating purified human CD4 T cells over 4 hours with 10 μg/mL Alemtuzumab in medium supplemented with 10% human AB serum in vitro…
Functionally Altered GPI-Anchor Negative Treg Following Alemtuzumab-Based T-Cell Depletion Are Associated with Acute Gvhd.
2012
Abstract Abstract 3059 Introduction: The monoclonal anti-CD52antibody Alemtuzumab is frequently used for T-cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT) to prevent graft versus host disease (GVHD). We previously demonstrated the long term persistence of functionally impaired glycosylphosphatidylinositol (GPI)-anchor negative effector T-cells in patients receiving high dose (100mg) Alemtuzumab in combination with a dose reduced conditioning regimen (Fludarabin + Melpahlan) (Meyer, Wagner et al. BMT 2010). Despite of Alemtuzumab-mediated TCD, half of our patients developed acute GVHD. Since regulatory T cells (Treg) play a major role for cont…
Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation
2000
The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR beta chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A Vbeta8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at …
MEF2C and SOCS2 in stemness regulation
2015
The physiologic stemness of hematopoietic stem cells (HSC) relies on mechanisms constitutively active under steady state and is fundamental to maintain a lifelong HSC reservoir. On the other side, similar stemness features sustained by partially overlapping molecular circuits, which have recently come into focus, confer aggressive aggressiveness in leukemia clones. Suppressor of Cytokine Signalling 2 (SOCS2) belongs to the SOCS family, comprising eight members (SOCS1–7 and CIS) with similar structures, which are induced upon JAK/STAT activation and function as negative regulators. Recent evidences have demonstrated that SOCS2 is endowed with immunological functions in differentiated cells b…
Advances in haploidentical stem cell transplantation for hematologic malignancies
2016
One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We als…
Prevention of chemotherapy-induced anemia and thrombocytopenia by constant administration of stem cell factor.
2011
Abstract Purpose: Chemotherapy-induced apoptosis of immature hematopoietic cells is a major cause of anemia and thrombocytopenia in cancer patients. Although hematopoietic growth factors such as erythropoietin and colony-stimulating factors cannot prevent the occurrence of drug-induced myelosuppression, stem cell factor (SCF) has been previously shown to protect immature erythroid and megakaryocytic cells in vitro from drug-induced apoptosis. However, the effect of SCF in vivo as a single myeloprotective agent has never been elucidated. Experimental Design: The ability of SCF to prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia was tested in a mouse model of cisplat…
Transmission of angioimmunoblastic T-cell lymphoma by bone marrow transplant
2014
Accidental transmission of lymphoma by bone marrow transplant is a rarely reported event [1–5], since candidates are only accepted for hematopoietic stem cell donation after a work-up that routinel...