scholarly journals Possible Impact of Cytomegalovirus-Specific CD8 + T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation

2017 ◽  
Vol 23 (7) ◽  
pp. 1046-1053 ◽  
Author(s):  
Justyna Ogonek ◽  
Pavankumar Varanasi ◽  
Susanne Luther ◽  
Patrick Schweier ◽  
Wolfgang Kühnau ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Reconstitution ◽  
Donor Chimerism

scholarly journals miR-625-3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183828 ◽  
Author(s):  
Kriti Verma ◽  
Nidhi Jyotsana ◽  
Ivonne Buenting ◽  
Susanne Luther ◽  
Angelika Pfanne ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Reconstitution

scholarly journals B and T Lymphocyte Attenuator Mediates Inhibition of Tumor-Reactive CD8+ T Cells in Patients After Allogeneic Stem Cell Transplantation

2012 ◽  
Vol 189 (1) ◽  
pp. 39-49 ◽  
Author(s):  
Willemijn Hobo ◽  
Wieger J. Norde ◽  
Nicolaas Schaap ◽  
Hanny Fredrix ◽  
Frans Maas ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation

Automated Generation of Antigen-Specific T Cells for Adoptive T Cell Therapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1177-1177
Author(s):  
Melanie Fahrendorff ◽  
Nanette von Oppen ◽  
Georg Rauser ◽  
Mario Assenmacher ◽  
Juergen Schmitz ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Closed System ◽  
Isolated Cells ◽  
Ifn Gamma ◽  
Cell Processing

Abstract Abstract 1177 The adoptive transfer of antigen-specific T cells can be a powerful tool for immunotherapy of malignant diseases or infectious complications after allogeneic stem cell transplantation (Riddell et al., 1992; Heslop et al. 2010). Human adenovirus (AdV), Epstein-Barr virus (EBV) or cytomegalovirus (HCMV) infections are frequent and often life-threatening complications post allogeneic stem cell transplantation. To reduce the time required to isolate antigen-specific T cells for adoptive transfer we have developed a method to isolate IFN-gamma-secreting CD4+ as well as CD8+ T cells after antigen-specific restimulation, the Cytokine Capture System IFN-gamma (CCS). Several preclinical studies demonstrate the efficient enrichment of functional CD4+ and CD8+ T cells specific for HCMV (Rauser et al., 2004), EBV (Hammer et al., 2007) or AdV (Feuchtinger et al. 2008) using the CCS. First clinical data of adoptively transferred HCMV-, EBV- or AdV-specific T cells into patients post allogeneic stem cell transplantation are very encouraging (Feuchtinger et al., 2010; Moosmann et al., 2010; Feuchtinger et al., 2006) with low T cell doses infused varying from 1–97×10e3 cells/kg. We have now developed a cell processing device for the automation of the CCS procedure. Antigen-specific stimulation, labeling with the CCS reagents, washing steps, cytokine capture, magnetic enrichment and potentially expansion of the isolated cells are performed fully automated in a closed system. At the beginning of the procedure all components including the cellular starting product, antigen(s), reagents, buffer, and media are connected to a sterile single-use closed system processing set in the device. Due to usage of sterile filters and sterile docking the whole process runs under sterile conditions. The cellular end product can be obtained in the medium/buffer of choice, with the desired cell concentration and volume. The cellular starting product can be leukapheresis or bone marrow and the yield of antigen-specific T cells depends on the frequency of IFN-gamma producing cells. When starting with 1×10e9 cells 1–20×10e5 HCMV-specific T cells could be isolated. Cell processing is possible overnight and the isolated cells might be used directly after enrichment or after a phase of in vitro expansion. Using this cell processing device, IFN-gamma secreting HCMV-specific T cells were enriched to the same purity (>80% IFN-gamma secreting CD4+ and CD8+ T cells) as with the semi-automated procedure. Cell loss during the procedure is markedly reduced, leading to an increased yield of IFN-gamma positive cells. An improved viability was observed resulting in better expansion rates. In conclusion, the automation in a closed system enables the fast and robust generation of antigen-specific T cells for adoptive therapy and will reduce clean room requirements. Disclosures: Fahrendorff: Miltenyi Biotec GmbH: Employment. von Oppen:Miltenyi Biotec GmbH: Employment. Rauser:Miltenyi Biotec GmbH: Employment. Assenmacher:Miltenyi Biotec GmbH: Employment. Schmitz:Miltenyi Biotec GmbH: Employment. Biehl:Miltenyi Biotec GmbH: Employment. Miltenyi:Miltenyi Biotec GmbH: Membership on an entity's Board of Directors or advisory committees.

Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3690-3697 ◽  
Author(s):  
Evren Özdemir ◽  
Lisa S. St. John ◽  
Geraldine Gillespie ◽  
Sarah Rowland-Jones ◽  
Richard E. Champlin ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Reconstitution ◽  
Cell Responses ◽  
Tetramer Staining ◽  
Cmv Reactivation ◽  
Cmv Antigenemia

Cytomegalovirus (CMV) infection causes significant morbidity and mortality in the setting of immunodeficiency, including the immune reconstitution phase following allogeneic stem cell transplantation (SCT). We assessed CMV-specific CD4+ and CD8+T-cell responses in 87 HLA-A*0201–positive (A2+) and/or B*0702-positive (B7+) allogeneic stem cell transplant recipients using HLA-peptide tetramer staining and cytokine flow cytometry (CFC) to examine the association of CMV-specific immune reconstitution and CMV antigenemia following SCT. Strong CMV-specific T-cell responses recovered in most subjects (77 of 87, 88%) after SCT. Frequencies of CMV-specific CD8+ T cells were significantly higher in those subjects who experienced early antigenemia relative to those who did not (2.2% vs 0.33%, P = .0002), as were frequencies of CMV-specific CD4+ T cells (1.71% vs 0.75%,P = .002). Frequencies of CMV-specific CD8+ T cells were also higher in subjects experiencing late antigenemia (2.4% vs 0.57%). When we combined tetramer staining and an assessment of cytokine production in a single assay, we found that individuals who experienced CMV antigenemia had lower tumor necrosis factor-α (TNF-α)–producing fractions of tetramer-staining CMV-specific CD8+ T cells than subjects who did not (25% vs 65%,P = .015). Furthermore, individuals at high risk for CMV reactivation, including patients with acute graft-versus-host disease and those receiving steroids, had low fractions of cytokine-producing CMV-specific CD8+ T cells (25% and 27%, respectively). These data suggest that the inability to control CMV reactivation following allogeneic SCT is due to the impaired function of antigen-specific CD8+ T cells rather than an inability to recover sufficient numbers of CMV-specific T cells.

scholarly journals Cytomegalovirus-specific CD8+ T-cells are associated with a reduced incidence of early relapse after allogeneic stem cell transplantation

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213739 ◽  
Author(s):  
Pavankumar Reddy Varanasi ◽  
Justyna Ogonek ◽  
Susanne Luther ◽  
Elke Dammann ◽  
Michael Stadler ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Early Relapse
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