4). The two populations were individually labeled with CellTrace and then co-cultured at the original ratio (one Treg to nine effector cells), combining either labeled Treg with unlabeled T-effector cells, or conversely labeled T-effector cells with unlabeled Treg cells. These experiments demonstrate that a very low frequency of Foxp3+ T cells arise from the labeled effector T-cell population, cultured alone or with labeled Treg cells, in the absence or presence of 1α25VitD3 (<2% at day 14; data not shown). These data suggest that 1α25VitD3 is not acting to enhance adaptive/activation-dependent

Foxp3 expression. Furthermore, across a dose titration of 1α25VitD3, Treg cell proliferation was only reduced at 10−6 M 1α25VitD3, whereas at all other concentrations proliferation Alectinib ic50 was unaffected or even enhanced (Fig. 6C and D). In contrast, proliferation of labeled effector T cells in co-culture was reduced at all concentrations of 1α25VitD3 click here tested (10−9–10−6 M 1α25VitD3; Fig. 6C and D).

These data imply that culture of T cells with 1α25VitD3 preferentially expands Treg over T-effector cells. Our earlier studies demonstrated that 1α25VitD3 enhances IL-10 expression by CD4+ T cells not only in culture, but also following ingestion of standard formulary doses of 1α25VitD3 by both steroid refractory asthma patients and healthy subjects [12, 14]. Subsequent work has demonstrated that no parallel increase in Foxp3 gene expression occurred in the same peripheral blood CD3+CD4+ T cells, analyzed directly ex vivo pre- and post-1α25VitD3 ingestion (data not shown). To investigate whether vitamin D might influence Foxp3 expression in the tissues, we analyzed the frequency of CD4+Foxp3+ cells in bronchoalveolar lavage (BAL) samples available from a pediatric severe asthma cohort under study, where serum 25-hydroxyvitamin D3 status was also being assessed (Supporting Information Table 1) [21]. Strikingly the majority of these patients showed a vitamin D status reflecting insufficiency (<75nmol/L) or deficiency (<50 nmol/L) [22]. A statistically significant correlation between serum vitamin

D status, and the frequency of CD4+Foxp3+ T cells in the BAL was observed (r = 0.71, p = 0.02), suggesting an in vivo correlate of our in vitro observations on the capacity of 1α25VitD3 to influence Foxp3+ Treg cell prevalence Clomifene (Fig. 7 and Supporting Information Fig. 5). Interest in enhancing Treg cells in patients is clearly driven by the therapeutic potential of these cells. An attractive approach would be the use of pharmacological agents such as 1α25VitD3, or vitamin D supplementation, to induce the expansion and/or maintenance of Treg cells. This approach is especially suited to ongoing chronic diseases such as asthma that occur at high prevalence, where a simple treatment such as vitamin D supplementation would be relatively safe, acceptable to patients, and cost effective.

Clearly, as low vitamin D status and its clinical consequences may be secondary to a host of factors, including advanced age, reduced mobility from disease, reverse causation cannot be excluded. Studies investigating the effect of migration and vitamin D supplementation on PD risk are lacking. There is a clear heritable component in PD. Genetic studies have pointed to a possible role of vitamin D in susceptibility to the disease. Polymorphisms in the VDR gene have been shown to associate with PD risk

in American and Korean cohorts, with the former cohort also showing an age of onset effect [138, 139]. The relatively small sample sizes and the inconsistent replication of SNPs in the VDR gene in discovery and validation sets dampen the impact of these findings. GWAS have identified an increasing number of candidate Barasertib risk genes in PD, several of which have VDR-binding sites closely associated with them raising the possibility that vitamin D may influence their expression. The biological relevance of a subset of these

susceptibility genes with associated VDR binding on brain function has been well delineated with evidence for roles in nigrostriatal dopaminergic neurotransmission, neurogenesis and neurite outgrowth, and neural ectodermal expression (especially within the marginal and subventricular zones) (see Table 2) [140-144]. Amyotrophic lateral sclerosis (ALS) is a progressive see more neurodegenerative disease affecting both the central and peripheral nervous systems [145]. ALS pathology reveals degeneration of motor neurones and corticospinal tracts, brainstem nuclei, and spinal cord anterior horn cells, with a subset of patients having intracytoplasmic transactive responsive DNA-binding protein inclusions (TDP-43) [146]. Multiple effector pathways are thought to contribute to ALS pathology including neurotrophic factor deficiency, glutamate toxicity, and damage from ROS [54]. Given that many of these effector

pathways are influenced by vitamin D in rodent models, there has been growing interest in the concept that this secosteroid may influence susceptibility to and disease progression in ALS. The epidemiological evidence incriminating vitamin D as a possible risk factor in ALS is sparse. The relatively either low population prevalence probably contributes but there may be no association. Season of birth observations have been conflicting with a few studies reporting excess births between April and July [147], and others reporting birth excess in between October and December (with a trough between April and July) [148]. A latitude gradient has been suggested, but the results are divergent. An American cohort outlining the geographic distribution of ALS using mortality data demonstrated a north-west to south-east gradient [149], a finding mirrored in a more recent study which found a higher ALS-associated death rate in more northern states [150].

Spleens from DENV-2-infected mice were surgically removed at different time-points and single cell suspensions were prepared. Approximately 0·5 × 106 to 1 × 106 spleen cells were incubated with either 10 μg/ml of the indicated peptide, RPMI-1640 medium (Gibco) or PMA (0·1 μg/ml) + ionomycin (1 μg/ml). Golgi plug (BD Biosciences, San Jose, CA) was added to each of the CHIR 99021 above samples and incubated at 37° for 6 hr. Cells

were washed with FACS buffer, blocked with Fc block (2.4G2) for 10 min and then surface stained with peridinin chlorophyll protein-Cy5.5-hCD45 (clone 2D1), phycoerythrin-Cy7-mCD45 (clone 30-F11), FITC-hCD3 (clone UCHT1), phycoerythrin-hCD8 (clone H1T8a) and Pacific Blue-hCD4 (clone RPAT4) antibodies for 20 min at room temperature. Cells were washed with FACS buffer, then permeabilized using Cytofix/Cytoperm buffer (BD Biosciences) and stained with allophycocyanin-hIFN-γ (clone B27) and Alexa700-TNF-α for 20 min at room temperature. Selleckchem Ridaforolimus In all experiments the viability marker LIVE/DEAD® Aqua (Molecular Probes, Eugene, OR) was added to exclude dead cells. All cell preparations were fixed with Cytofix (BD Biosciences). Cytokine levels were also assessed by ELISA; 0·5 × 106 to 1 × 106 spleen cells from DENV-2-infected mice

were incubated with either 10 μg/ml of the indicated peptide, RPMI-1640 medium (Gibco) or PMA (0·1 μg/ml) + ionomycin (1 μg/ml) and incubated at 37° for 96 hr. Culture supernatants were collected and IFN-γ level was determined by IFN-γ ELISA (R&D Systems, Minneapolis, MN). Levels of DENV-2 envelope (E) protein-specific antibody in the serum of DENV-infected

engrafted, uninfected engrafted and non-engrafted mice were determined using a standard ELISA. Ninety-six-well microplates were coated overnight with 100 ng/well of DENV-2 E protein (Hawaii Biotech, Aiea, HI) or 1 : 40 dilution of DENV-2-infected Vero cell lysate. The plates were blocked with 1% bovine serum albumin for 90 min and a 1 : 20 dilution of sera diluted with PBS was added to the wells for 1 hr. Plates were washed with PBS containing 0·1% Tween-20. Horseradish peroxidase-labelled goat anti-human IgM or IgG (Bethyl Laboratories Inc., Montgomery, Dipeptidyl peptidase TX) was added as the secondary antibody. TMB Solution (Sigma-Aldrich Inc., St Louis, MO) was used as the substrate. The enzyme reaction was stopped by addition of 1 m HCl and the plates were read at 450 nm. Positive controls included sera from a known DENV-positive human. Sera from uninfected engrafted and non-engrafted mice were used as negative controls. All assays were carried out in duplicate or triplicate. Splenocytes from DENV-2 S16803-infected or naive mice were stimulated in vitro with CpG (2·5 μg/ml) + interleukin-2 (1 μg/ml) and Epstein–Barr virus (50 μl/ml). Supernatants of stimulated splenocytes collected 14 days after in vitro stimulation were tested for DENV-specific IgM antibodies and for DENV neutralization activity.

The limitations of the study include the low number of probable and proven cases in the cohort, which might have led to worse results than some other studies in the literature. However, it is a valuable experience to discuss as it may demonstrate the caveats of empirical approach as well as the difficulty of implementing a GM and CT based pre-emptive strategy in a true cohort, which we face every day in routine clinical

practice. In conclusion, GM testing has been a major advance in the medical care of the patients with haematological LBH589 solubility dmso malignancies. However, each centre should evaluate the usefulness of this test in its own conditions. The specific characteristics of the environment such as renovations that might increase exposure of the patients to Aspergillus species and result in anti-Aspergillus antibodies, as well as certain therapeutic practices, i.e. use of piperacillin-tazobactam in febrile neutropenic patients, rate of utilisation of imaging techniques and other microbiological diagnostic procedures, and the non-ideal settings of real life may profoundly influence the yield of this important serological marker for early diagnosis. The authors want to thank Infectious Diseases INCB024360 purchase research nurse Nimet Simsek for

her efforts in specimen collection and Muge Durusu for the preparation of figures and tables. This study was supported with a grant from the Scientific and Technical Research Council of Turkey, Health Sciences Research Grant Group. “
“Serum (13)-β-D-glucan (BG) is increasingly used as diagnostic marker for invasive fungal infections. Exposure to gauze may lead to false-positive BG assays. The role of BG is unclear in thermally injured patients who frequently require extensive gauze coverage; therefore, we prospectively evaluated BG levels in burn-injured patients. Serum BG levels were measured in 18 burn patients immediately before application of the first dressing and 12 h after. Patients were stratified by extent of total body surface area (TBSA) requiring gauze coverage: <20%, 20–39%, 40–60% and >60%. BG levels were obtained

from patients with next non-burn trauma as controls. BG results were positive (>80 pg ml−1) in 9/18 (50%) patients at baseline and in 8/18 (44%) 12 h after application of the first dressing. BG levels were positive in 1/5 (20%) of patients with <20% TBSA requiring gauze and in 10/13 (77%) with ≥20% (P < 0.05). None of the control patients had positive BG at any time point and none of the patients had candidemia at baseline. Mean serum BG levels decreased (19.44 pg ml−1) after gauze placement. False-positive serum BG elevations are common in this patient population. Positivity correlates with extent of TBSA injured, but is not impacted by the gauze itself. "
“Aspergillus pleural empyema is a rare but often fatal infection complicating thoracic surgery.

No specific treatment for recurrent IgA nephropathy is currently available. However, Torin 1 ic50 three studies from Japan showed that a tonsillectomy improved clinical and histological damage in patients with IgA recurring after kidney transplantation.[7, 9, 10] Hotta et al.[7] suggested that tonsillectomy is an efficacious treatment for recurrent IgA nephropathy, especially in the mild or early stage. Recurrent IgA nephropathy can occur at any time after transplantation. The early detection of mesangial IgA deposition and IgA nephropathy

using long-term protocol biopsy may improve graft survival. Calcineurin inhibitors have long been the standard of care for immunosuppression after solid organ transplantation. However, CNI sometimes have adverse effects, including nephrotoxicity, hypertension, hyperlipidemia, glucose intolerance and hirsutism.[11, 21] Chronic CNI-related nephrotoxicity occurs several months after renal transplantation and progresses with

time. The histological indicators of chronic CNI-induced nephrotoxicity are hyaline arteriolopathy, striped interstitial fibrosis, GDC-0199 purchase and tubular atrophy. In advanced cases, the entire wall is replaced by the hyaline material and the lumen is severely narrowed.[22] Both cyclosporine and tacrolimus produced similar fibrogenic effects in the kidney and a similar pattern of nephrotoxicity.[23] Assessment of long-term protocol biopsies is useful not only for detection of CNI nephrotoxicity, but also for follow-up after withdrawal of a CNI regimen. Despite several longer-term follow-up analyses of CNI withdrawal, few studies have investigated the long-term follow-up with protocol biopsies.[12, 23, 24] Previously, we showed that CNI withdrawal can be safely implemented in stable renal transplant recipients and might lead to improved patient outcomes. However, in the same study, we found no association between CNI withdrawal and improvement of the histological lesions.[24] Also, Naesens et al.[25] pointed that neither tacrolimus dose nor measures of systemic exposure Celecoxib were associated

with lesions of CNI nephrotoxicity. A recent retrospective study of low-dose cyclosporine therapy suggested that the CNI was not the only factor involved in the development of arteriolar hyalinosis.[12] CNI-based regimens remain our most widely used and powerful strategy, so further studies should focus on elucidation of additional specific evidence of CNI toxicity. BK polyomavirus nephropathy (BKVN) has a reported incidence of 1–10%. Although the prevalence is relatively low, activation of BKV has become an important cause of kidney transplant failure.[26, 27] Protocol biopsies may be a useful tool to detect viral infections such as BKVN because early diagnosis is necessary to resolve infection and prevent chronic damage. The importance of protocol biopsies in the diagnosis of BKVN was shown by Buehrig et al.

The prevalence of ZnT8Ab varied between 58% [11] and 83% [7] in newly diagnosed T1D patients with a

general lower prevalence in the Chinese population (24%) [12]. Consistently, ZnT8R autoantibodies (ZnT8RAb) (50–54%) appear to be more frequent than ZnT8W autoantibodies (ZnT8WAb) (41–50%) [13-15] and ZnT8Q autoantibodies (ZnT8QAb) (32–36%) [14, 15] in White people. Although ZnT8QAb are found in combination with ZnT8RAb or ZnT8WAb, it NVP-AUY922 research buy is rare to find patients who have only ZnT8QAb and no other islet autoantibody [16]. Importantly, ZnT8Ab have been found to react differently to the ZnT8 cytoplasmic fragment used for autoantibody detection dependent on the amino acid at position 325 [13]. The amino acid at position 325 in the COOH-terminal part of ZnT8 is controlled by the single nucleotide polymorphism (SNP) rs13266634 in the gene of ZnT8, SLC30A8 [17]. This genetic Alpelisib manufacturer polymorphism causes an amino acid change in position 325 from arginine (CGG) present

in 69% compared to 31% for tryptophan (TGG) in healthy controls [18] and was not found to be associated with T1D in the genetic consortium (GM) genome-wide association scanning [19]. Despite the absence of an association with T1D, several authors have independently reported a correlation between the rs13266634 genotype and the autoantibody specificity of ZnT8RAb and ZnT8WAb [13, 20] [9, 21]. T1D patients with the C allele more often than expected had ZnT8RAb, and patients with the T allele had ZnT8WAb. As 30–44% of ZnT8Ab-positive subjects react with all three variants [13], that is, despite that subject is homozygous for R/R, there may still be autoantibodies that react with ZnT8W [15]. The character of the residue 325 in Fossariinae ZnT8 was thought to represent a conformational epitope [22]. However, the epitope-specific reactivity to the ZnT8 268–369 in vitro transcription translation product is poorly investigated. The aims of the present study were therefore to 1) determine the immunogenicity of 15-mer short ZnT8 (318–331) peptides in mice with either R or W at position 325; 2) test the

ability of these short ZnT8 peptides to compete with radiolabelled (ZnT8 268–369) long proteins in binding to patient sera specific for either ZnT8RAb or ZnT8WAb; and 3) test the ability of the unlabelled long ZnT8 (268–369) proteins to compete with radiolabelled long ZnT8 (268–369) proteins in binding to patient sera specific for either ZnT8RAb or ZnT8WAb. Fifteen-mer peptides (short) of ZnT8R, ZnT8W and ZnT8Q (aa 318–331) covering sequences NH2-CHVATAASRDSQVVR-COOH) with R, W or Q, respectively, in the aa position 325 (Fig. 1) were synthesized by a standard Solid-phase peptide synthesis (SPPS) with 9-fluorenylmethyloxycarbonyl group (Fmoc) and determined by mass-spectrometry (MS) at Innovagen AB, Lund, Sweden. AB.

To apply our results in the above-mentioned ways, the core of our future work will be identifying peaks that represent in our classification tree by 2-dimensional gel electrophoresis and tandem MS, then validating the identified

peptides by antibody-based tests such as ELISA and Western blot. Our study indicated that MALDI-TOF MS combined with magnetic beads and bioinformatics tools was an effective technology for constructing classification tree model. In particular, we have established a powerful model that can accurately discriminate patients with active TB from non-TB H 89 individuals. m/z 8561 and 8608 might play an important role not only in the pathogenesis of active TB but also in the regulation of active TB status. The study was supported by a grant for infectious diseases from Ministry of Health, China to XC (2008ZX10003-012). We declare that we have no conflict of interest to disclose. “
“The syncytiotrophoblast (STB) of human placenta constitutively produces and secretes extracellular vesicles of different size, morphology and function that enter the maternal circulation, and

participate in the maternal–fetal cross-talk during pregnancy. Syncytiotrophoblast-derived microvesicles/microparticles (STBM) are larger microvesicles (0.2–2 μm) shed by the apical plasma membrane of the STB as a result of cell activation and turnover. Simultaneously with the STBM shedding, the STB produces and secretes exosomes – nanosized (30–100/150 nm) membrane-bound microvesicles that originate from the endosomal compartment. They convey

cell–cell contact ‘by learn more proxy’ transporting signals/packages of information between donor and recipient cells locally or/and at a distance. STBM and exosomes, delivered directly in the maternal blood surrounding the chorionic villi of the placenta, have contrasting biological functions. While the exosomes are immunosuppressive down regulating maternal immunity in pluripotent CYTH4 ways, the main effects of STBM on the maternal immune system are pro-inflammatory, immune activating, and pro-coagulant. Since both STBM and exosomes are present in the maternal circulation throughout normal pregnancy logical questions are what is the net effect of these vesicles on the maternal immune system and is this effect beneficial or detrimental to pregnancy. In this review, the current knowledge about placenta-derived extracellular vesicles with a main focus on exosomes is summarized and discussed. In a concluding remark, a hypothetical proposal on how STBM and exosomes might interact in pregnancy is discussed and a way to evaluate this interaction is suggested. “
“GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known.

neoformans antigens to primed T cells after the immune response had peaked and the immunoglobulin

switch from the initial IgM had also occurred, thereby helping the development of a more effective protective Th1 immune response. In summary, the present study demonstrates that opsonized live Cabozantinib ic50 yeasts of C. neoformans activate eosinophils, inducing the expression of MHC class I, MHC class II and costimulatory molecules. Furthermore, although the secretion of proinflammatory cytokines is also increased, the production of oxygen and nitrogen radicals is down-regulated. These activated eosinophils can also stimulate CD4+ and CD8+ T cells to produce an antigen-specific immune response, thus creating a Th1 microenvironment. These results suggest that, in addition to their role as effector cells, eosinophils may also serve as specific APCs during fungal infection. Moreover, the fact that eosinophils are able to communicate with T cells suggests that they

could be involved in the adaptive immune response to C. neoformans. The present work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica (PICT 33326); Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (PIP 6327); Secretaría Sirolimus mw de Ciencia y Tecnología (SeCyT), Universidad Nacional de Córdoba (Grant 69/08); and Ministerio de Ciencia y Tecnología de la Provincia de Córdoba (Grant 2008). A. P. Garro DOK2 and J. L. Baronetti are PhD fellows of Consejo Nacional de Investigaciones Científicas y Técnicas, and L. S. Chiapello and D. T. Masih are members of the Research Career of Consejo Nacional de Investigaciones Científicas y Técnicas. We would like to thank native speaker,

Paul Hobson for revision of the manuscript. The authors have no conflicts of interest to disclose. Figure S1. Flow cytometry analysis of the percentage of contaminating cells between eosinophil populations. Figure S2.Cryptococcus neoformans-pulsed eosinophils do not promote the production of Th 2 type cytokines by Ag-specific CD4+ and CD8+ T cells. “
“The implication of B lymphocytes in the immunopathology of multiple sclerosis (MS) is increasingly recognized. Here we investigated the response of B cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored the frequency of TLR7-induced IgM and IgG-secreting cells in MS patients to the levels found in healthy donors, showing a specific deficiency in the TLR7 pathway. However, no difference was observed in the TLR9 response. Furthermore, in MS-derived PBMCs, TLR7-mediated production of IL-6 and the ex vivo expression of B-cell-activating factor of the TNF family, two crucial cytokines for B-cell differentiation and survival, were induced by IFN-β.

In addition, damaged

tubular cells upregulate multiple inflammatory cytokines as well as Toll like receptors (TLRs), costimulatory molecules, contributing to inflammation or immune activation. Both innate and adaptive immune system are activated and play important roles in Kinase Inhibitor Library injury and repair following I/R. Activation of innate immune system comprises trafficking of neutrophil, macrophage, NK cells and NKT cells and also activation of resident kidney dendritic cells. These cells of innate immunity participate in initial kidney injury by producing multiple enzymes such as protease, myeloperoxidase or proinflammatory cytokines. In contrast to CD4+ T cells that are known to contribute to injury, CD4+ CD25+ Foxp3+ regulatory T cells with antinflammatory property are thought to promote repair. Better understanding of exact pathogenetic mechanisms of injury and repair following I/R injury is needed for the development of preventive or therapeutic strategies. YUZAWA YUKIO, HAYASHI HIROKI, HASEGAWA MIDORI Department of

Nephrology, Fujita Health University School of Medicine, Japan Although the KDIGO GL for AKI 2013 contains clear indicators for early or mild AKI, the time lag before serum Cr elevation in response to changes in Atezolizumab research buy acute-phase GFR leads to delays in AKI diagnosis. A group of kidney-specific urinary biomarkers such as NGAL, IL18, KIM-1 and L-FABP has recently been identified. Clinical application of these biomarkers to enable earlier AKI diagnosis is eagerly anticipated. Since the diagnostic potential of each biomarker is limited, it is important to create a panel that simultaneously measures multiple biomarkers to increase diagnostic

accuracy by combining the strengths of each and compensating for their shortcomings. The clinical use of AKI biomarkers has yet to progress past the 3-mercaptopyruvate sulfurtransferase level of prospective observational cohort studies during clinical research regarding biomarker evaluation. RCTs are required to further evaluate each biomarker regarding clinical usefulness, prognosis, and cost-effectiveness. DOI KENT1, NOIRI EISEI2, IWAGAMI MASAO2, NANGAKU MASAOMI2, YAHAGI NAOKI1 1Department of Emergency and Critical Care Medicine, The University of Tokyo, Japan; 2Department of Hemodilaysis and Apheresis, The University of Tokyo, Japan Acute blood purification plays a crucial role in the treatment of acute kidney injury (AKI) occurring in an ICU because no specific drug that can treat AKI sufficiently is clinically available. Many clinical studies have examined treatment settings of acute blood purification and provided verifiable results, but some critical issues remain unresolved. This presentation will overview the evidence related to 1) optimal therapeutic dose of renal replacement therapy (RRT), 2) early initiation of RRT, and 3) potential role of endotoxin absorption for septic AKI.

In contrast, in the same cultures, there was abundant IFN-γPos Teff expansion, resulting on day 3 in very low aTreg:aTeff ratios ranging from 0·02

to 1·2 (Fig. 6d). Together, these data provide evidence to suggest that both in vitro and in vivo exposure to IFN-α can potentially cause an unbalanced generation of activated Teffs at the expense of Treg activation. The maintenance of immune homeostasis relies on the co-existence of different cell types with unique and sometimes divergent functions, which are co-ordinately activated to achieve initial effector functions in response to pathogens and subsequent immune inactivation after pathogen clearance. However, the mechanisms that R788 define the sequential activation/expansion of effector and regulatory cells are still incompletely understood. In this study, we focused on the potential role of IFN-I in controlling the dynamic balance between Treg and Teff activation during polyclonal T-cell activation in human PBMC. The main findings in the study are that (i) anti-CD3 activation of PBMC induces prominent FoxP3 expression on CD4+ cells and the generation of two major subtypes of FoxP3+ cells, CD4+ FoxP3HI IFN-γNeg IL-2Neg aTregs and CD4+ FoxP3Low/Neg IFN-γPos IL-2Pos aTeffs; (ii) IFN-I, Metformin either exogenously added or endogenously generated by double-stranded

RNA stimulation or from plasma of patients with SLE, limits the generation of aTregs, (iii) IFN-α (but not IFN-β) favours Teff expansion, leading to a reduced aTreg:aTeff ratio; (iv) inhibition of IL-2 production during T-cell activation is a potential mechanism involved in IFN-α-induced suppression of aTreg induction; and (v) the in vivo exposure to IFN-α tilts the balance between aTregs and aTeffs towards Teff upon ex vivo expansion of PBMC. Taken together, these findings provide evidence Florfenicol to suggest that, by inhibiting Treg activation and proliferation, the transient IFN-α production in response to a viral infection may co-ordinate the sequential generation of

aTeffs and aTregs, and that the Teff:Treg balance may be altered under conditions of chronic IFN-α stimulation. A potential role of IFN-α in controlling the dynamic generation of regulatory T cells in vivo, both in humans and in mice, is supported by different observations. (i) The transient period of immunosuppression that follows the recovery of primary viral infections coincides with the decline in the production of IFN-I and an increase in the number of Tregs;22,23 (ii) when measles virus is introduced into a mouse deficient in the IFNα/β receptor, this results in significantly higher numbers of Tregs;40 (iii) in vivo treatment of mice with poly(I:C) leads to a decrease in the number of Tregs,41 and (iv) chronic disorders characterized by persistent IFN-α stimulation are frequently associated with low numbers of Tregs and with autoimmunity.