Superiority of bone marrow-derived dendritic cells over monocyte-derived ones for the expansion of regulatory T cells in the macaque

Regulatory T cells (Treg) have been identified as playing a pivotal role in the control of tolerance and in the suppression of pathologic immune responses in autoimmune diseases, transplantation, and graft-versus-host disease. Treg expanded ex vivo by dendritic cells could be potential reagents to promote antigen-specific tolerance in vivo. However, in vivo studies have been carried out mostly in rodents and will need validation in primates before clinical application. We characterized macaque dendritic cell derived either from bone marrow with and without prior CD34+ cell selection (BMDC), or from CD14+ peripheral blood mononuclear cells (Mo-DC). We demonstrate that with a semi-mature phenotype, BMDC are superior to Mo-DC in their capacity to expand freshly isolated allogeneic macaque CD4+ CD25+ CD127- Foxp3+ Treg in vitro in the presence of interleukin-2. Moreover, the expanded Treg maintain their phenotype and suppressive activity. These data provide a step toward the use of macaque dendritic cell to expand Treg for future preclinical testing.     

Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

INTRODUCTIONMatrix metalloproteinases(MMPs)comprise a group of zinc and calcium-dependent endopeptidases that exhibit differential proteolytic activity against extracellular matrix(ECM)proteins.Based on substrate specificity,MMPs have been classically div…     

An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML.     

Critical Requirement for Graft Passenger Leukocytes in Allograft Tolerance Induced by Donor Blood Transfusion

Tolerance to a vascularized allograft can be induced in adultanimals by pregraft donor-specific blood transfusion (DST). Mechanismsunderlying this effect appear to depend on unresponsiveness ofalloreactive T-helper cells. In this study, we examined the roles ofDST and cellular components of the allograft that are important ininducing T-cell unresponsiveness in a rat model. DST alone did nottolerize alloreactive recipient T-helper cells, but the combination ofDST and heart allograft induced profound inhibition of the antidonorproliferative response in spleen but not in lymph node cells. Whenheart allografts were depleted of passenger leukocytes by pretreatingthe donor with cyclophosphamide or by parking the graft for 2 months ina tolerant recipient, tolerance induction in DST-treated recipients wasabrogated. Tolerance could then be restored in a majority ofDST-treated recipients of passenger leukocytes depleted grafts byinjecting them at the time of grafting with donor, but not third-party,dendritic cells. This indicates that graft passenger leukocytes, mostlikely dendritic cells, are required for DST-induced allografttolerance.     

The quality of radiology services in five Latin American countries]

OBJECTIVE: To determine the correlation between certain quality indicators for imaging services and the accurate interpretation of radiological exams for four frequent complaints: breast lumps, gastrointestinal discomfort, back pain, and symptoms of tuberculosis. METHODS: Twenty-six radiology services in Argentina, Bolivia, Colombia, Cuba, and Mexico were assessed. The mammography and conventional radiographic/fluoroscopic equipment used in selected services were evaluated utilizing common protocols, data sheets, testing instruments, phantoms, and calibrated dosimetry systems. The studies were performed in medium-complexity facilities. Informed consent was obtained from all patients studied, and the confidentiality of results was guaranteed. The following parameters were documented: type of facility (public vs. private); population covered; patient workload; radiological and image-processing equipment and supplies; education and training of professional and technical staff; quality assurance and preventive maintenance programs, and adherence to radiation safety standards. The performance of x-ray units, image receptors and processors; darkroom and image viewing conditions; patient doses and image quality, were determined using standardized parameters in all cases. Independent panels of radiologists, recognized as experts by the local radiological society, assessed the quality of the clinical images obtained and performed a radiological interpretation for each patient using the same films and clinical history available to the institution's imaging physicians. The agreement between the panel of expert's reports and those of local radiologists was taken as an indicator of the radiological diagnostic accuracy. RESULTS: Analyses were carried out of 366 mammograms, 343 radiological procedures for gastrointestinal complaints, 319 X-rays of the spinal column, and 157 chest radiographs. The agreement between the radiological interpretation of the panel of experts and of the local physician ranged from 70% to 100%, except in the case of spinal column films in Cuba (57.8%) and of mammograms in Mexico (33.3%), which the panel of experts found to be among those having the poorest quality. There was a significant positive correlation between the accuracy of the radiological interpretation and the quality of the radiological images. Image quality showed a positive correlation with the technicians' level of education and training. Studies performed in services that had automatic film processors and that complied with the indicators established for screen-film contact yielded better images and a higher proportion of studies with concordant results. More than 50% of the viewboxes did not satisfy the quality criteria for luminance and homogeneity. CONCLUSIONS: A good quality image is critical to achieving an accurate diagnosis. Emphasis should be placed on the continuing education of radiology technicians and on the acquisition and maintenance of adequate equipment and accessories, especially viewboxes, intensifying screens, and automatic film processors, given the impact they have on image quality.     

Rat Spleen Dendritic Cells Express Natural Killer Cell Receptor Protein 1 (NKR-P1) and Have Cytotoxic Activity to Select Targets via a Ca2+-dependent Mechanism

Dendritic cells (DC) are a subset of leukocytes whose major function is antigen presentation. We investigated the phenotype and function of enriched (95–98.5%) rat DC. We show that both spleen and thymus DC express the natural killer cell receptor protein 1 (NKR-P1) as a disulfide linked homodimer of 60 kD. Freshly isolated DC express a low level of NKR-P1, which is strongly upregulated after overnight culture. Spleen, but not thymus DC, were able to kill the NK-sensitive YAC-1 cell line in vitro, and since this killing was Ca²⁺ dependent, a Fas ligand–Fas interaction was probably not involved. Besides their potent antigen-presenting function, DC can thus be cytotoxic for some tumor targets.     

DNASE1L3 deficiency,new phenotypes,and evidence for a transient type I IFN signaling

Journal of Clinical Immunology - Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3...