SARS-CoV-2-specicific humoral immunity in convalescent patients with mild COVID-19 is supported by CD4 T-cell help and negatively correlated with Alphacoronavirus-specific antibody titer.

This study aimed at investigating the nature of SARS-CoV-2-specific immunity in patients with mild COVID-19 and sought to identify parameters most relevant for the generation of neutralizing antibody responses in convalescent COVID-19 patients. In the majority of the examined patients a cellular as well as humoral immune response directed to SARS-CoV-2 was detected. The finding of an anti-SARS-CoV-2-reactive cellular immune response in healthy individuals suggests a pre-existing immunity to various common cold HCoVs which share close homology with SARS-CoV-2.

Circulating Dickkopf1 Parallels Metabolic Adaptations and Predicts Disease Trajectories in Patients With COVID-19.

Context And Aims: Coronavirus disease 19 (COVID-19) trajectories show high interindividual variability, ranging from asymptomatic manifestations to fatal outcomes, the latter of which may be fueled by immunometabolic maladaptation of the host. Reliable identification of patients who are at risk of severe disease remains challenging. We hypothesized that serum concentrations of Dickkopf1 (DKK1) indicate disease outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals.

Recruitment of highly cytotoxic CD8 T cell receptors in mild SARS-CoV-2 infection.

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8 T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals.

Antigen-shift in varicella-zoster virus-specific T-cell immunity over the course of Fingolimod-treatment in relapse-remitting multiple sclerosis patients.

Background: Fingolimod (FTY) applied as treatment regimen of relapsing-remitting multiple sclerosis (RRMS) induces downregulation of sphingosine-1-phosphate receptors on the lymphocytes. As a result CC chemokine receptor type 7 (CCR7) expressing lymphocytes are retained within the peripheral lymph nodes thus suppressing their accumulation into the cerebrospinal fluid of multiple sclerosis (MS) patients and hampering disease progress. Unfortunately, MS patients treated with FTY suffer from an increased incidence of varicella-zoster virus (VZV) infections which has been associated with a decrease of VZV immediate early 63 (IE63)-specific T-cell immunity.

PRAME peptide-specific CD8 T cells represent the predominant response against leukemia-associated antigens in healthy individuals.

Antigen-specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia-associated antigen (LAA)-specific T cells in HIs still limits such an approach for tumor therapy. Therefore, we have investigated T-cell responses against prominent candidates comprising Wilms' tumor protein 1 (WT1), preferentially expressed antigen in melanoma (PRAME), Survivin, NY-ESO, and p53 by screening PBMCs from HIs using intracellular IFN-γ staining following provocation with LAA peptide mixes.

Clinical grade manufacturing of genetically modified, CAR-expressing NK-92 cells for the treatment of ErbB2-positive malignancies.

Background: The NK-92/5.28.z cell line (also referred to as HER2.

Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

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 drug-refractory 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.

NK-92: an 'off-the-shelf therapeutic' for adoptive natural killer cell-based cancer immunotherapy.

Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however always remain variable due to individual differences of donors or patients.

Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation.

Recently, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been suggested as an alternative to MSCs for the treatment of various inflammatory disorders. However, while a first case report observed beneficial therapeutic effects of repeated MSC-EV infusions in a patient with therapy-refractory graft-versus-host disease, in vitro findings revealed that MSC-EVs were significantly less immunosuppressive than their parental cells. In this study, we compared the immunosuppressive potency of MSCs derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs), with their secreted EVs in a standardized lymphocyte proliferation assay (LPA).

Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor.

Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen.

Clinical-scale isolation of 'minimally manipulated' cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease.

Background Aims: Reactivation of cytomegalovirus (CMV) after hematopoietic stem cell transplantation remains a major cause of morbidity despite improved antiviral drug therapies. Selective restoration of CMV immunity by adoptive transfer of CMV-specific T cells is the only alternative approach that has been shown to be effective and non-toxic. We describe the results of clinical-scale isolations of CMV-specific donor lymphocytes with the use of a major histocompatibility (MHC) class I peptide streptamer-based isolation method that yields minimally manipulated cytotoxic T cells of high purity.

Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy.

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols.

Gamma irradiation preserves immunosuppressive potential and inhibits clonogenic capacity of human bone marrow-derived mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of graft-versus-host and autoimmune diseases. Here, by virtue of their immunosuppressive effects, they are discussed to exhibit inhibitory actions on various immune effector cells, including T lymphocytes that promote the underlying pathology. While it becomes apparent that MSCs exhibit their therapeutic effect in a transient manner, they are usually transplanted from third party donors into heavily immunocompromised patients.

Validation of cord blood split products prepared by an automated method.

Objectives: In this study, we studied whether the contents of the two compartments of automatically processed cord blood (CB) units are comparable with respect to cell counts and viability and therefore suitable for clinical therapy.

Background: CB-derived stem cells are increasingly used for allogeneic transplantation. Many centres prepare the transplants by automated methods allowing to split the product into two portions.

PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease.

Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance.

Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation.

Background: Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic stem cell transplantation. For the clearance of CMV, CD8+ T cells are pivotal.

Study Design And Methods: Here, the novel streptamer technology was used at good manufacturing practice (GMP) level for adoptive transfer of CMV-specific T cells into acute leukemia patients with recurrent high CMV antigenemia after allogeneic stem cell transplantation.

Enumeration of viable CD34(+) cells by flow cytometry in blood, bone marrow and cord blood: results of a study of the novel BD™ stem cell enumeration kit.

Background Aims: Enumeration of CD34(+) cells in leukocyte-rich cell suspensions is important for clinical decision-making in stem cell transplantation. Single-platform flow cytometry assays offer the significant advantages of speed and reproducibility, and have therefore become the gold standard in stem cell enumeration. The clinical community has recently defined the need for stem cell enumeration kits that incorporate viability dyes.

Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response.

Maintenance of protective humoral immunity depends on the generation and survival of antibody-secreting cells. The bone marrow provides niches for long-term survival of plasma cells generated in the course of systemic immune responses in secondary lymphoid organs. Here, we have analyzed migratory human plasma blasts and plasma cells after secondary vaccination with tetanus toxin.

Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus.

Objective: In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.

Methods: We used flow cytometry to analyze expression of the T cell-specific inducible costimulator (ICOS) and its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE patients.

CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations.

Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38.

Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus.

Objective: To investigate the distribution of peripheral B cell subpopulations of children with active and inactive systemic lupus erythematosus (SLE) compared with healthy controls.

Methods: Peripheral B cell subpopulations of 11 children with SLE (6 with active and 5 with inactive disease) and 14 age matched normal healthy children were analysed. Active disease was diagnosed in children with a flare of SLE, who received treatment by i.

Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus.

Objective: Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters. In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of disease activity was assessed.

Methods: The distribution of B cell subsets was determined by fluorescence-activated cell sorting analysis and assessed in relation to the autoantibody profile, disease activity measured by the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure scores, disease duration, and therapy.