Blood dendritic cell levels and phenotypic characteristics in relation to etiology of end-stage heart failure: implications for dilated cardiomyopathy.

Background: Dysregulation of dendritic cell (DC) mediated immune responses towards auto-antigens, is considered an important feature in the maintenance of experimentally induced heart failure (HF). In order to evaluate the role of blood DCs in cardiomyopathies of different origins, we examined myeloid (mDC) and plasmacytoid (pDC) subset levels and maturation characteristics, according to HF severity and etiology in humans.

Methods: Absolute numbers of mDCs and pDCs in 12 New York Heart Association (NYHA) class-II, 28 NYHA class III-IV HF patients and 18 healthy controls, were studied by 4-colour whole blood flow cytometry.

Peripheral blood manipulation significantly affects the result of dendritic cell monitoring.

It has been postulated that the plasmacytoid/myeloid dendritic cell ratio (pDC/mDC) reflects immune reactivity, and can therefore be used to monitor transplant recipients. We investigated the influence of Ficoll-Paque separation and PBMC cryopreservation on the pDC/mDC ratio and the expression of maturation markers, e.g.

Stable T-cell reactivity after successful tapering of azathioprine in HLA-identical living-related kidney transplant recipients despite minor histocompatibility antigen mismatches.

Background: Human leukocyte antigen (HLA)-identical living-related (LR) kidney transplant recipients often receive the standard regimen of immunosuppression. We wondered whether these patients should be exposed to the side effects of these drugs any longer. Safe tapering of immunosuppression should not result in rejection and high donor-directed T-cell responses.

Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease.

Background: Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon.

FTY720 treatment of kidney transplant patients: a differential effect on B cells, naïve T cells, memory T cells and NK cells.

FTY720 alters lymphocyte recirculation and homing by interfering with S1P receptors on lymphocytes, possibly in combination with chemokine receptors, and induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney transplant patients, we analyzed by flow cytometry the effect of FTY on the number of NK cells, monocytes, naïve (CCR7+) T cells, memory (CCR5+) T cells and B cells. Patients treated with 0.

Altered chemokine receptor profile on circulating leukocytes in human heart failure.

Chemokines and their receptors have been implicated in the pathogenesis of different forms of heart failure (HF). We examined CC- and CXC-chemokine receptor expression in fresh peripheral blood leukocyte populations from 24 end-stage HF patients consisting of coronary artery disease (CAD; n = 6) and hypertrophic cardiomyopathy (HCM; n = 7) or idiopathic dilated cardiomyopathy (IDCM; n = 8) or valvular disease (VD; n = 3) and compared the data with 18 healthy controls. Levels of CCR1, 2, 3, 4, 5, and 7, and CXCR1, 2, 3, and 4 were measured by flow cytometry, and the expression profile was assessed as molecules of equivalent soluble fluorochrome units as well as frequency (percentage) of CD3+, CD4+, and CD8+ T cells and monocytes or granulocytes.

Calcineurin inhibitor withdrawal in stable kidney transplant patients decreases the donor-specific cytotoxic T lymphocyte precursor frequency.

Background: In a prospective study, calcineurin inhibitors (CNI) were withdrawn in patients two years after kidney transplantation. We questioned whether stopping CNI had an effect on the donor-specific reactivity, as CNI might hinder immune responses leading to graft acceptance.

Methods: We measured the donor-specific cytotoxic T lymphocyte (CTL) precursor frequency (CTLpf) in 54 patients before and after withdrawal of CNI.

The direct and indirect allogeneic presentation pathway during acute rejection after human cardiac transplantation.

Alloreactive T cells may be activated via a direct or an indirect antigen presentation pathway. We questioned whether the frequency of interferon (IFN)-gamma producing cells determined by enzyme-linked immunospot (ELISPOT) assay is an effective tool to monitor the direct and/or indirect presentation pathway. Secondly, we wondered whether early and late acute rejection (AR) are associated with both pathways.

Impaired circulating dendritic cell reconstitution identifies rejecting recipients after clinical heart transplantation independent of rejection therapy.

Objective: Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx).

Methods: Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx.

The effects of renal transplantation on circulating dendritic cells.

The effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in peripheral blood of 24 kidney allograft recipients before and after transplantation, and in 23 donors before and after kidney donation. All patients were treated with tacrolimus, mycophenolate mofetil and prednisone.

Preferential depletion of blood myeloid dendritic cells during acute cardiac allograft rejection under controlled immunosuppression.

Allo-Ag presentation to Ag-specific T-lymphocytes by donor or recipient dendritic cells (DCs) induces acute rejection (AR) after solid organ transplantation. It is postulated that myeloid (mDC) and plasmacytoid (pDC) subsets circulate differentially between bone marrow, heart and lymphoid tissues after cardiac transplantation (HTx). We investigated peripheral blood DC subset distribution, maturation and lymphoid homing properties in relation to endomyocardial biopsy (EMB) rejection grade after clinical HTx.

Vitamin E-coated dialyzer membranes downregulate expression of monocyte adhesion and co-stimulatory molecules.

Background: In patients on chronic hemodialysis leukocyte activation has been related to the impaired function of the immune system. In this study we investigated if the vitamin E-coated dialyzer membrane could reduce monocyte activation thereby improving cellular immunity.

Methods: This hypothesis was tested in a prospective crossover trial in which 14 stable hemodialysis patients were switched from the baseline hemophane dialyzer to a vitamin E-coated and thereafter a polysulphone dialyzer membrane or vice versa.

Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients.

Background: Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination.

Peripheral blood dendritic cells in human end-stage heart failure and the early post-transplant period: evidence for systemic Th1 immune responses.

Objectives: Dendritic cells (DCs) are antigen presenting cells that play a central role in inflammation, allograft rejection and immune tolerance. Myeloid (mDC) and plasmacytoid (pDC) subsets regulate immune reactions by polarising naive T-helper cells into a Th1 or Th2 response, respectively. In this study we examined total peripheral blood DCs, mDC and pDC subsets in chronic heart failure (CHF) and clinical heart transplantation (HTx).

The frequency of interferon-gproducing cells reflects alloreactivity against minor histocompatibility antigens.

Background: In human leukocyte antigen (HLA)-identical living-related renal transplant recipients, no donor-specific alloreactivity can be detected in regular tests (mixed lymphocyte culture, helper T-lymphocyte precursor frequencies, cytotoxic T-lymphocyte precursor frequencies) to identify patients responding to minor histocompatibility antigens (mHag). We questioned whether a more sensitive method like the Elispot-assay could be more appropriate.

Methods And Results: Peripheral blood mononuclear cells (PBMC) from 16 HLA-identical living-related kidney transplant patients 3 months (range, 2 weeks to 5 months) after transplantation were tested for the frequency of interferon (IFN)-gamma producing cells by the Elispot-assay.

A broad and strong humoral immune response to donor HLA after implantation of cryopreserved human heart valve allografts.

Cryopreserved human heart valves are used for valve replacement in patients with congenital or acquired heart disease. Although no blood group or human leukocyte antigens (HLA) matching is performed and no immunosuppression is administered, the clinical results are relatively good. After valve replacement, the majority of the patients develop HLA antibodies, whereas a smaller group of patients shows valve-related events at the long term after right ventricular outflow tract reconstruction.

Frequencies of donor-reactive helper T lymphocytes correlate with rejection of aortic valve allografts in rats.

Background And Aims Of The Study: Human valve allografts are commonly used in cardiac surgery for congenital and acquired valve diseases. Particularly in the pediatric population, these allografts are prone to fail in the long term, and require replacement. In part, this failure may be due to immunological phenomena.

The presence of immune stimulatory cells in fresh and cryopreserved donor aortic and pulmonary valve allografts.

Background And Aim Of The Study: Heart valve allografts (HVA) used for valve replacement or ventricular outflow tract reconstruction may suffer from structural deterioration due to donor-specific immune responses. The presence of immune stimulatory cells, including dendritic cells and activated endothelial cells, has not been studied thoroughly in aortic or pulmonary HVA. The presence and distribution of these cells in both aortic and pulmonary HVA, before and after cryopreservation, was analyzed immunohistochemically.

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation.

Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity.

Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.

Background: A reliable immunological assay for quantification of donor-specific alloreactivity to identify patients at risk for future allograft rejection would be a helpful tool in organ transplantation. Therefore, we questioned whether the T cell reactivity in patients measured before transplantation was predictive for the occurrence of acute rejection during the first year after kidney transplantation.

Methods: The pretransplant T cell reactivity of peripheral blood mononuclear cells to donor and third-party antigens was tested in mixed lymphocyte cultures, and to tetanus toxoid.

Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation.

Implantation of cryopreserved human donor heart valves for either congenital or acquired cardiac disease has been performed since the last three decades. Although the clinical outcome is good, long-term valve degeneration resulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the factors involved in this process.

Immunological aspects of fresh and cryopreserved aortic valve transplantation in rats.

Background: The influence of immune activation on valve allograft degeneration remains unclear. We studied the combined effect of major histocompatibility complex (MHC)-incompatibility and cryopreservation on valve performance, histomorphology, and tissue antigenicity in rats.

Methods: Fresh or cryopreserved allogeneic aortic valves from WAG (RT1u) rats were transplanted to DA (RT1a) recipients and syngenic transplants served as controls.

Reassuring effect of pravastatin on natural killer cell activity in stable renal transplant patients.

Background: Administration of pravastatin soon after transplantation successfully lowers cholesterol levels, whereas a reduced number of acute rejection episodes is accompanied by a decrease in natural killer (NK) cell activity. As a consistent low NK cell activity caused by pravastatin might impair tumor surveillance leading to cancer, we studied the effect of pravastatin on NK cell activity in stable renal transplant patients.

Methods: From 14 cyclosporine (CsA)-treated and 11 azathioprine (AZA)-treated patients with hypercholesterolemia, more than 1 year after kidney transplantation, we determined NK cell number and cytotoxic activity before, and at 6 and 12 weeks after, initiating pravastatin treatment.