Search results for "Lymphocyte Depletion"
showing 10 items of 31 documents
STAT1 Isoforms Differentially Regulate NK Cell Maturation and Anti-tumor Activity
2020
Natural killer (NK) cells are important components of the innate immune defense against infections and cancers. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that is essential for NK cell maturation and NK cell-dependent tumor surveillance. Two alternatively spliced isoforms of STAT1 exist: a full-length STAT1α and a C-terminally truncated STAT1β isoform. Aberrant splicing is frequently observed in cancer cells and several anti-cancer drugs interfere with the cellular splicing machinery. To investigate whether NK cell-mediated tumor surveillance is affected by a switch in STAT1 splicing, we made use of knock-in mice expressing either only the STAT1α (S…
Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.
2017
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor-or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drugrefractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D+ repl; n = 28) or T-cell-depleted (D+ depl; n = 16) …
Lack of requirement for CD8+ cells in recovery from and resistance to experimental autoimmune encephalomyelitis.
1995
Abstract Experimental autoimmune encephalomyelitis (EAE) is a model of T-cell mediated autoimmune disease. Active disease is mediated by myelin basic protein specific CD4+T-cells, whose adoptive transfer can also induce passive disease. In the Lewis rat EAE is a transient disease inducing lasting resistance to rechallenge. The mechanisms of recovery and resistance are poorly understood. CD8+suppressor T-cells have mostly been thought to be central, especially in resistance to reinduction of the disease. In this study we showed by complete depletion of CD8+cells that this subset does not influence either recovery or resistance to EAE in the Lewis rat. This was further confirmed by depleting …
Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell tr…
2007
Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (1 microg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (30%). However, the number of tumor reactive (CD107a+…
Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis
2013
Depletion of naive T cells from donor leukapheresis products (LPs) aims at the reduction of alloreactivity, while preserving memory T-cell reactivity (for example, to pathogens). This study established the immunomagnetic depletion procedure under clean room conditions using CD45RA beads and analyzed LPs of six donors for cell composition and functional immune responses. CD45RA depletion resulted in 3.4-4.7 log (median 4.4) reduction of CD45RA(+) T cells, thereby eliminating naive and late effector T cells. B cells were also completely removed, whereas significant proportions of NK cells, monocytes and granulocytes persisted. CD45RA-depleted LPs contained effector and central memory CD4(+) a…
Selective Depletion of Alloreactive T Lymphocytes Using Patient-Derived Nonhematopoietic Stimulator Cells in Allograft Engineering
2008
Background. Selective depletion of alloreactive T cells in vitro results in efficient graft-versus-host disease prophylaxis in allogeneic hematopoietic stem-cell transplantation, but it is accompanied by increased recurrence of leukemia. To spare donor T-cell-mediated graft-versus-leukemia immunity against hematopoiesis-restricted minor histocompatibility (minor-H) antigens, we explored the use of patient-derived nonhematopoietic antigen-presenting cells (APC) as allogeneic stimulators for selective allodepletion in leukemia-reactive donor T-cell lines. Methods. Primary keratinocytes, dermal fibroblasts, and bone marrow fibroblasts were generated from skin biopsies and diagnostic bone marro…
Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplant…
2001
We investigated whether a T cell-reduced allogeneic stem cell transplant (SCT) with minimal conditioning and subsequent donor lymphocyte infusions (DLI) could reduce the incidence and severity of GVHD while retaining stable engraftment. Five patients with hematological malignancies (three MM, one CLL, one Chediak-Higashi syndrome) were conditioned with TBI (200 cGy). One patient additionally received fludarabine (120 mg/m(2)). CsA and mofetyl-mycophenolate (MMF) were administered to prevent GVHD. All patients were grafted with >3 x 10(6)/kg highly purified CD34(+) cells together with 2 x 10(6)/kg CD3(+) cells (three patients) or 1 x 10(5)/kg CD3(+) cells (two patients). Quick hematopoietic …
Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell–depleted reduced-intensity transplantation
2006
AbstractAllogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5- to 6-log reduction in CD8 T cells. Of 23 high-risk patients with h…
Partial T Cell-Depleted Peripheral Blood Stem Cell Transplantation from HLA-Identical Sibling Donors for Patients with Severe Aplastic Anemia
2019
We analyzed the outcomes of 26 consecutive patients with acquired severe aplastic anemia (SAA) undergoing peripheral blood stem cell transplantation (PBSCT) with partial ex vivo T cell depletion with a targeted T cell dose from HLA-identical sibling donors. The median patient age was 37 years (range, 3 to 63 years). Four patients with uncontrolled pneumonia at the time of transplantation died, on days +1, +2, +21, and +26. All evaluable patients engrafted, with a median time to neutrophil recovery of 11 days (range, 10 to 14 days) and a median time to platelet recovery of 19 days (range, 8 to 53 days). Two patients had transient grade I acute graft-versus-host disease (GVHD) with skin invol…
Depletion of Alloreactive Donor T Lymphocytes by CD95-Mediated Activation-Induced Cell Death Retains Antileukemic, Antiviral, and Immunoregulatory T …
2007
In allogeneic hematopoietic stem cell transplantation (AHSCT) graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect are closely but not invariably linked. Thus, harnessing donor lymphocyte mediated GVL immunity and separating it from GVHD is of particular interest. Based on results obtained in murine models we have explored the CD95-mediated activation-induced cell death (AICD) strategy to selectively deplete alloreactivity in human donor T lymphocytes in vitro. Following stimulation of CD3(+) T cells isolated from HLA-A* 0201-positive donors with HLA or minor histocompatibility antigen mismatched hematopoietic or nonhematopoietic cells in the presence of agonistic anti-CD…