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1.
Int J Pharm ; 569: 118575, 2019 Oct 05.
Article in English | MEDLINE | ID: mdl-31356956

ABSTRACT

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24 h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300 nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0 µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofx in human cell models (A549 and Wi-38) at 24 h and 48 h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.


Subject(s)
Anti-Infective Agents , Drug Carriers , Eugenol , Nanoparticles , Ofloxacin , A549 Cells , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacokinetics , Cell Survival/drug effects , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Liberation , Eugenol/administration & dosage , Eugenol/chemistry , Eugenol/pharmacokinetics , Humans , Lipids/administration & dosage , Lipids/chemistry , Lipids/pharmacokinetics , Lung/metabolism , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Ofloxacin/administration & dosage , Ofloxacin/chemistry , Ofloxacin/pharmacokinetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development
2.
Colloids Surf B Biointerfaces ; 167: 73-81, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29627680

ABSTRACT

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation.


Subject(s)
Anticonvulsants/chemistry , Carbamazepine/chemistry , Lipids/chemistry , Nanoparticles/chemistry , Nanostructures/chemistry , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Calorimetry, Differential Scanning , Carbamazepine/administration & dosage , Carbamazepine/pharmacokinetics , Dogs , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Madin Darby Canine Kidney Cells , Mice , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , Nanostructures/ultrastructure , Particle Size , Thermogravimetry , X-Ray Diffraction
3.
Bone Marrow Transplant ; 53(1): 39-43, 2018 01.
Article in English | MEDLINE | ID: mdl-28991245

ABSTRACT

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms, Second Primary/etiology , Transplantation Conditioning/adverse effects , beta-Thalassemia/complications , Female , Humans , Male , Middle Aged , Neoplasms, Second Primary/pathology
4.
Bone Marrow Transplant ; 52(9): 1225-1232, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28319074

ABSTRACT

The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated. Meanwhile, several drugs used for the treatment of hematologic malignancies or for other purposes have been shown to upregulate the number and function of Tregs in vivo. In the near future, both ex vivo or in vivo expanded T cells are likely to enter the therapeutic armamentarium of clinical transplantation.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , T-Lymphocytes, Regulatory/metabolism , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Animals , Humans
6.
Bone Marrow Transplant ; 50 Suppl 2: S63-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26039211

ABSTRACT

Relapse is still the major cause of failure of allogeneic stem cell transplantation in high-risk acute leukemia patients. Indeed, whoever the donor and whatever the transplantation strategy, post-transplant relapse rates are ~30%, which is hardly satisfactory. The present phase 2 study analyzed the impact of adoptive immunotherapy with naturally occurring FoxP3+ T-regulatory cells (2 × 10(6) per kg) and conventional T lymphocytes (1 × 10(6) per kg) on prevention of GvHD and leukemia relapse in 43 high-risk adults undergoing full-haplotype mismatched transplantation without any post-transplant immunosuppression. Ninety-five percent of patients achieved full-donor type engraftment. Only 6/41 patients (15%) developed ⩾ grade II acute GvHD. Specific CD4(+) and CD8(+) for opportunistic pathogens emerged significantly earlier than after standard T-cell-depleted haplo-transplantation. The probability of disease-free survival was 0.56. At a median follow-up of 46 months (range 18-65 months), only 2/41 evaluable patients have relapsed. The cumulative incidence of relapse was significantly lower than in historical controls (0.05 vs 0.21; P = 0.03). These results demonstrate that the immunosuppressive potential of Tregs can be used to suppress GvHD without loss of the benefits of GvL activity. Humanized murine models provided insights into the mechanisms underlying separation of GvL from GvHD.


Subject(s)
Adoptive Transfer , Graft vs Host Disease , HLA Antigens , Hematopoietic Stem Cell Transplantation , Leukemia , T-Lymphocytes, Regulatory/transplantation , Acute Disease , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Humans , Leukemia/mortality , Leukemia/therapy , Male , Middle Aged , Recurrence , Survival Rate
9.
Br J Pharmacol ; 169(8): 1652-71, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23714011

ABSTRACT

UNLABELLED: Adult haematopoietic stem/progenitor cells (HSPCs) constitute the lifespan reserve for the generation of all the cellular lineages in the blood. Although massive progress in identifying the cluster of master genes controlling self-renewal and multipotency has been achieved in the past decade, some aspects of the physiology of HSPCs still need to be clarified. In particular, there is growing interest in the metabolic profile of HSPCs in view of their emerging role as determinants of cell fate. Indeed, stem cells and progenitors have distinct metabolic profiles, and the transition from stem to progenitor cell corresponds to a critical metabolic change, from glycolysis to oxidative phosphorylation. In this review, we summarize evidence, reported in the literature and provided by our group, highlighting the peculiar ability of HSPCs to adapt their mitochondrial oxidative/bioenergetic metabolism to survive in the hypoxic microenvironment of the endoblastic niche and to exploit redox signalling in controlling the balance between quiescence versus active cycling and differentiation. Especial prominence is given to the interplay between hypoxia inducible factor-1, globins and NADPH oxidases in managing the mitochondrial dioxygen-related metabolism and biogenesis in HSPCs under different ambient conditions. A mechanistic model is proposed whereby 'mitochondrial differentiation' is a prerequisite in uncommitted stem cells, paving the way for growth/differentiation factor-dependent processes. Advancing the understanding of stem cell metabolism will, hopefully, help to (i) improve efforts to maintain, expand and manipulate HSPCs ex vivo and realize their potential therapeutic benefits in regenerative medicine; (ii) reprogramme somatic cells to generate stem cells; and (iii) eliminate, selectively, malignant stem cells. LINKED ARTICLES: This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8.


Subject(s)
Adult Stem Cells/cytology , Adult Stem Cells/metabolism , Mitochondria/metabolism , Adult , Cell Differentiation , Cell Lineage , Energy Metabolism , Glycolysis , Humans , Models, Biological , Oxidation-Reduction , Oxidative Phosphorylation
10.
Clin Exp Immunol ; 173(2): 195-206, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23607751

ABSTRACT

Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc-mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, ß-galactosidase (ß-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4(+) cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc-MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0-G1 phase, without significant differences between SSc and HC. SSc-MSCs showed an increased positive ß-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, ß-Gal staining increased significantly in SSc-MSCs. On the contrary, doxorubicin abolished p21 activation and elicited p53 induction both in SSc- and HC-MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-ß-related transcripts and their protein levels were significantly higher in SSc-MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells, increasing surface expression of CD69 and restoring the regulatory function which is impaired in SSc. Increased activation of the IL-6 pathway observed in our cells might represent an adaptive mechanism to senescence, but preserving some specific cellular functions, including immunosuppression.


Subject(s)
Mesenchymal Stem Cells/immunology , Scleroderma, Systemic/immunology , T-Lymphocytes, Regulatory/immunology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Cell Proliferation/drug effects , Cell- and Tissue-Based Therapy , Cells, Cultured , Cellular Senescence/drug effects , Cellular Senescence/immunology , Coculture Techniques , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Doxorubicin/pharmacology , Humans , Immunomodulation , Interleukin-6/genetics , Interleukin-6/metabolism , Lectins, C-Type/metabolism , Scleroderma, Systemic/therapy , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Tumor Suppressor Protein p53/metabolism , beta-Galactosidase/metabolism
11.
Prostate Cancer Prostatic Dis ; 16(1): 56-61, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22850906

ABSTRACT

BACKGROUND: Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions and ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor (VEGF), interleukin (IL)-10, IL-1ß, alpha-1-antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case-control study have been investigated. METHODS: SNPs of VEGF (rs699947), ACT (rs1884082), IL-1ß (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay. RESULTS: Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF, the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation. CONCLUSIONS: SNPs in VEGF, IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.


Subject(s)
DNA Methylation/genetics , Genetic Predisposition to Disease/genetics , Inflammation/genetics , Prostatic Neoplasms/genetics , Aged , Alleles , Genotype , Glycine N-Methyltransferase/genetics , Humans , Inflammation/pathology , Interleukin-10/genetics , Interleukin-1beta/genetics , Male , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Prostatic Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , alpha 1-Antichymotrypsin/genetics
12.
Mini Rev Med Chem ; 12(10): 959-70, 2012 Sep 01.
Article in English | MEDLINE | ID: mdl-22420574

ABSTRACT

CNS drug development is characterized by an especially high attrition rate, despite clear unmet medical needs in the field of neuro-pharmacology and significant investment in R of novel CNS drug treatments. Here, we overview the issues underlying the intrinsic difficulty of CNS drugs development, including obstacles of pharmacokinetic nature and lack of predictivity of preclinical tests. We highlight current efforts to overcome these limitations, with an emphasis on modeling opportunities towards early recognition of CNS candidates (stressing the possibilities of multi-target directed ligands or "magic shotguns") and different approaches to improve CNS bioavailability.


Subject(s)
Central Nervous System Agents/chemistry , Central Nervous System Agents/pharmacology , Central Nervous System Diseases/drug therapy , Drug Discovery/methods , Animals , Central Nervous System/drug effects , Computer-Aided Design , Humans
13.
Genes Immun ; 13(2): 197-201, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21866115

ABSTRACT

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.


Subject(s)
Lymphoma, Non-Hodgkin/genetics , Polymorphism, Genetic , Toll-Like Receptor 9/genetics , Female , Genetics, Population , Humans , Lymphoma, Non-Hodgkin/epidemiology , Male , Middle Aged , Risk Factors
14.
Bone Marrow Transplant ; 45(11): 1645-52, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20173782

ABSTRACT

T helper (Th) 17 cells have emerged as important mediators in infectious and inflammatory diseases and, recently, in transplant rejection. We analyzed the associations between five common genetic variants in the IL-23/Th17 signaling pathway, namely in IL17A, IL17F and IL23R genes, and clinical outcome in T cell-depleted allogeneic SCT (allo-SCT). In the multivariate analysis, variants in IL23R and IL17A genes were the most important prognostic factors. Thus, patient GA genotype at rs11209026 in IL23R was associated with improved overall survival (hazard ratio (HR)=0.48; P=0.028) and, in donor, with decreased risk of fungal infections (P=0.05). In contrast, patient TC and CC genotypes at rs8193036 in IL17A gene were associated with increased risk of CMV infection (HR=3.68; P=0.011) and patient acute GVHD (HR=7.08; P=0.008), respectively. These results suggest that genetic variants in the IL-23/Th17 inflammatory pathway are important prognostic factors for the clinical outcome of allo-SCT. Although validation studies are ultimately required, our results would suggest the potential usefulness of IL-23/Th17 genotyping in donor selection and patient evaluation.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Interleukin-17/genetics , Interleukin-23/genetics , Lymphocyte Depletion , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Child , Disease-Free Survival , Female , Genotype , Humans , Interleukin-17/metabolism , Interleukin-23/metabolism , Male , Middle Aged , Prognosis , T-Lymphocytes/cytology , Young Adult
15.
Int J Immunopathol Pharmacol ; 22(3): 567-72, 2009.
Article in English | MEDLINE | ID: mdl-19822073

ABSTRACT

Inhibitors of tumor necrosis factor-alpha have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-alpha molecule. These drugs include etanercept, a soluble TNF-alpha receptor antagonist, three anti-TNF-alpha antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-alpha biological-mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogenetic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases/drug therapy , Inflammation/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/pharmacokinetics , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Autoimmune Diseases/immunology , Certolizumab Pegol , Etanercept , Humans , Immunoglobulin Fab Fragments/therapeutic use , Immunoglobulin G/therapeutic use , Inflammation/immunology , Infliximab , Polyethylene Glycols/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Treatment Outcome
16.
Clin Exp Immunol ; 156(2): 246-53, 2009 May.
Article in English | MEDLINE | ID: mdl-19292855

ABSTRACT

Although CD4(+)/CD25(+) T regulatory cells (T(regs)) are a potentially powerful tool in bone marrow transplantation, a prerequisite for clinical use is a cell-separation strategy complying with good manufacturing practice guidelines. We isolated T(regs) from standard leukapheresis products using double-negative selection (anti-CD8 and anti-CD19 monoclonal antibodies) followed by positive selection (anti-CD25 monoclonal antibody). The final cell fraction (CD4(+)/CD25(+)) showed a mean purity of 93.6% +/- 1.1. Recovery efficiency was 81.52% +/- 7.4. The CD4(+)/CD25(+bright) cells were 28.4% +/- 6.8. The CD4(+)/CD25(+) fraction contained a mean of 51.9% +/- 15.1 FoxP3 cells and a mean of 18.9% +/- 11.5 CD127 cells. Increased FoxP3 and depleted CD127 mRNAs in CD4(+)CD25(+)FoxP3(+) cells were in line with flow cytometric results. In Vbeta spectratyping the complexity scores of CD4(+)/CD25(+) cells and CD4(+)/CD25(-) cells were not significantly different, indicating that T(regs) had a broad T cell receptor repertoire. The inhibition assay showed that CD4(+)/CD25(+) cells inhibited CD4(+)/CD25(-) cells in a dose-dependent manner (mean inhibition percentages: 72.4 +/- 8.9 [ratio of T responder (T(resp)) to T(regs), 1:2]; 60.8% +/- 20.5 (ratio of T(resp) to T(regs), 1:1); 25.6 +/- 19.6 (ratio of T(resp) to T(regs), 1:0.1)). Our study shows that negative/positive T(reg) selection, performed using the CliniMACS device and reagents, enriches significantly CD4(+)CD25(+)FoxP3(+) cells endowed with immunosuppressive capacities. The CD4(+)CD25(+)FoxP3(+) population is a source of natural T(reg) cells that are depleted of CD8(+) and CD4(+)/CD25(-) reacting clones which are potentially responsible for triggering graft-versus-host disease (GvHD). Cells isolated by means of this approach might be used in allogeneic haematopoietic cell transplantation to facilitate engraftment and reduce the incidence and severity of GvHD without abrogating the potential graft-versus-tumour effect.


Subject(s)
CD4-Positive T-Lymphocytes/cytology , Forkhead Transcription Factors/immunology , Interleukin-2 Receptor alpha Subunit/immunology , Adult , CD4-Positive T-Lymphocytes/immunology , Forkhead Transcription Factors/genetics , Humans , Immunomagnetic Separation , Immunophenotyping/methods , Interleukin-2 Receptor alpha Subunit/analysis , Interleukin-5 Receptor alpha Subunit/analysis , Interleukin-7 Receptor alpha Subunit/genetics , Leukapheresis/methods , Middle Aged , Phenotype , Reverse Transcriptase Polymerase Chain Reaction/methods , Spectral Karyotyping/methods
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