Search results for "T cell"
showing 10 items of 2228 documents
Redirected EBV-Specific Stem Cell-Memory and Central-Memory CD8+ T Lymphocytes Exhibit Effective and Sustained Antileukemic Immunity to Acute Myeloid…
2014
Abstract Introduction: Adoptive cellular therapy (ACT) of donor-derived cytolytic T lymphocytes (CTL) directed to leukemia or herpesvirus has proven promising to improve antiviral and antileukemic immunity in patients following allogeneic hematopoietic stem cell transplantation (AHSCT). However, durable clinical responses are often hampered by detrimental graft-versus host (GvH) reactivity and limited persistence of transferred, fully differentiated antileukemic effector T cells (TEFF). We thus explored memory and tumoricidal features of in vitro generated EBV-specific stem cell-memory T cells (TSCM) and central-memory T (TCM) cells, T cell-receptor (TCR) redirected to primary acute myeloid…
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation.
2012
Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanoma…
Therapeutic Vaccination of Hematopoietic Cell Transplantation Recipients Improves Protective CD8 T-Cell Immunotherapy of Cytomegalovirus Infection
2021
Reactivation of latent cytomegalovirus (CMV) endangers the therapeutic success of hematopoietic cell transplantation (HCT) in tumor patients due to cytopathogenic virus spread that leads to organ manifestations of CMV disease, to interstitial pneumonia in particular. In cases of virus variants that are refractory to standard antiviral pharmacotherapy, immunotherapy by adoptive cell transfer (ACT) of virus-specific CD8+ T cells is the last resort to bridge the “protection gap” between hematoablative conditioning for HCT and endogenous reconstitution of antiviral immunity. We have used the well-established mouse model of CD8+ T-cell immunotherapy by ACT in a setting of experimental HCT and mu…
TH17 cells mediate pulmonary collateral priming
2010
Background Our laboratory has shown that inhalational sensitization to new antigens is facilitated through an ongoing T H 2-polarized inflammation of the lung, a phenomenon we call "collateral priming." Objective We were interested to analyze whether a T H 1-polarized pulmonary inflammation also facilitates priming toward new antigens and which cytokine or cytokines are involved. Methods T H 1-polarized T cells were generated in vitro and transferred into congenic mice. Mice were challenged initially with cognate antigen and an unrelated antigen; consecutively, they received cognate antigen or the secondary antigen. Airway inflammation, antigen-specific IgG2a levels, and airway hyperrespons…
B?cells are not required for T?cell priming in low zone tolerance to contact allergens and contact hypersensitivity
2004
Low zone tolerance (LZT) to contact allergens is induced by epicutaneous exposure to haptens in subsensitizing doses resulting in an inhibition of contact hypersensitivity (CHS), which, in contrast, occurs after sensitization with immunogenic doses of allergens. Performing the protocol of tolerance induction resulted in robust LZT to allergens in B cell-deficient mice in vivo, indicating that B cells are not required for the induction and effector phase of LZT. However, CHS reactions in vivo were restricted in B cell-deficient mice as compared to wild-type (WT) mice. In contrast, analysis of hapten-specific T cell activation in vitro revealed a strong proliferative response of T cells deriv…
CD4+CD25+ Regulatory T Cells and TGF-Beta in Mucosal Inflammation
2008
Transforming growth factor-beta (TGF-beta) is an anti-inflammatory cytokine which plays a key role in the maintenance of the immune system homeostasis. Indeed the abrogation of the TGF-beta signaling in immune cells leads to autoimmunity and inflammation in several organs including the gut. TGF-beta acts at multiple levels to maintain the immune system in check. However, TGF-beta has been recently shown to play a key role in the peripheral generation and function of CD4+CD25+ regulatory T cells, a subset of suppressive lymphocytes involved in the control of effector T cell activation and proliferation. Consistently abrogation of Tregs maturation as observed in different systems leads to a p…
Transcriptional analysis distinguishes breast implant-associated anaplastic large cell lymphoma from other peripheral T-cell lymphomas
2019
Breast implant-associated anaplastic large cell lymphoma is a new provisional entity in the revised World Health Organization classification of lymphoid malignancies, the pathogenesis and cell of origin of which are still unknown. We performed gene expression profiling of microdissected breast implant-associated anaplastic large cell lymphoma samples and compared their transcriptional profiles with those previously obtained from normal T-cells and other peripheral T-cell lymphomas and validated expression of selected markers by immunohistochemistry. Our results indicate that most breast implant-associated anaplastic large cell lymphomas exhibit an activated CD4+ memory T-cell phenotype, whi…
Phenotype and functional changes of Vγ9/Vδ2 T lymphocytes in Behçet's disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation an…
2010
Introduction: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) that has been introduced recently for Behcet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vγ9/Vδ2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity. Methods: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vγ9/Vδ2 T lymphocytes by means of fluorescence-activated cell sorter …
Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells
2015
Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg), a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before and after interferon-beta therapy. We compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using a humanized mouse model. We found that CD4+ and CD8+ T cells of therapy-naive MS patients were resistant to Treg-mediated suppression. Treg resistance is associated with an augmented IL-6 product…
Value of bone marrow biopsy in the diagnosis of essential thrombocythemia.
2004
Background and Objectives. Essential thrombocythemia (ET) is a Philadelphia chromosome-negative chronic myeloproliferative disorder (CMPD) whose diagnosis, according to the Polycythemia Vera Study Group (PVSG) criteria, does not include histopathological data. The new WHO classification of CMPD has supplied new diagnostic guidelines which highlight the value of histopathology and facilitate a more precise differentiation of ET from reactive conditions and other CMPD. Design and Methods. Bone marrow biopsies from 142 adult patients diagnosed with ET according to PVSG criteria were evaluated using the new WHO classification. Megakaryocyte morphology and arrangement, amount of fibrosis and a c…