The use of

The use of KU-57788 clinical trial statins in treating KD may be beneficial due to its observed immunomodulatory properties, including the inhibition of T cell proliferation and cytokine production as well as inhibiting MMP-9 production, suggesting that statins may have benefit beyond that of cholesterol-lowering in Kawasaki disease. More study is needed to determine the safety and efficacy of this class of therapeutic agents in young children. This study was funded by operating grants from the Canadian Institutes of Health Research (MOP-81378)

and the Heart and Stroke Foundation of Canada (T6365). R.S.M.Y. is a recipient of an Investigator Award from the Arthritis Society of Canada and BWM is the holder of the CIBC World Markets Children’s Miracle research chair. All authors have no conflicts of interest. Fig. S1. Cytotoxicity assay. Mouse vascular smooth muscle cells (MOVAS) cells were cultured [Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS), sodium pyruvate, non-essential amino acid, R428 cell line 2 mM L-glutamine

and 10 mM HEPES] for 6 h in a 96-well culture plate with 25 ng/ml recombinant mouse tumour necrosis factor (TNF)-α (eBioscience, San Diego, CA, USA), and with either various atorvastatin concentrations or of the drug vehicle, dimethyl sulphoxide (DMSO). After the incubation period, cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) using a commercial kit, following the manufacturer’s protocol (Roche Applied Science, Mannheim, Germany). Open and solids bars represent cultures in the presence of atorvastatin and corresponding concentrations of DMSO, respectively. “
“Peripheral blood monocyte (PBM) subsets play different AZD9291 purchase roles in inflammatory response and tissue remodelling.

The aim of this study was to investigate how allergen challenge affects the number of circulating PBMs in Dermatophagoides pteronyssinus (Dp) allergic patients (Dp-APs). Among 34 Dp-APs challenged, in 22 patients significant bronchoconstriction was demonstrated [responders (Rs)], while in 12, only upper respiratory symptoms were seen [non-responders (NRs)]. Twelve healthy, non-atopic subjects were used as controls (HCs). Expression of CD14, CD16 and CCR4 was evaluated by flow cytometry on the whole-blood samples before (T0), 6 h (T6) and 24 h (T24) after the challenge. Plasma concentrations of CCL2, CX3CL1 and CCL17 were evaluated using ELISA. At T0, the mean percentage of CD14++ CD16+ PBMs in Rs (35.4%; 95%CI 26.9–43.9%) was significantly greater than in HCs (14.6%; 95%CI 7.3–21.8%; P = 0.006) and in NRs (17.5%; 95%CI 9.6–25.4%; P = 0.001). The baseline number of CD14++ CD16+ PBMs correlated with airway hyper responsiveness (AHR) (r = −0.507; 95%CI −0.834 to −0.432, P < 0.001). At T24, the number of CD14++ CD16+ PBMs significantly decreased in Rs but not in NRs and the numbers inversely correlated with plasma CCL17 concentration.

Several research groups are studying

Several research groups are studying Selleckchem Everolimus donor treatment and it may be applied clinically in the near future. However, our experimental model could not be transferred directly to a cadaveric donor transplant model, because brain death of the donor has not been considered. Brain death is a strong proinflammatory event that results in the activation of several pathways [54].

However, we believe that the model could be clinically useful for those patients with living donors who require prolonged bench surgery, or for those patients included in donor pair programmes requiring a longer time of cold ischaemia. As there is no evidence of immunosuppression to donors in living donors, this issue should be debated within a bioethical framework. To our knowledge, this is one of the few studies showing evidence of a lower I/R injury with combined immunosuppressive treatment of donors using a syngeneic rat model. The use of immunosuppressive drugs administered Wnt activity to donors has attenuated

the I/R injury process and this was demonstrated by a marked necrosis and apoptosis decrease in renal tubular epithelial cells. Further studies based on this exploratory study would describe the use of immunosuppressive treatment to the donor to improve the quality of the organ to be transplanted. The authors thank Professor Dr Enrique Portiansky for his assistance in the quantification of optical densities and areas of IHC. The authors of this manuscript have no conflicts Y-27632 cell line of interest to disclose. “
“Secretory proteins of Mycobacterium tuberculosis are the major immunomodulators of the host immune response. Open reading frame (ORF) Rv2626c, encoding a conserved hypothetical protein eliciting a strong humoral immune response in patients with tuberculosis (TB), was shown to be up-regulated upon infection in mice under hypoxic conditions. We now show that recombinant Rv2626c protein (rRv2626c) can bind to the surface of murine macrophages and elicit the type-1 immune response, as manifested by nitric oxide (NO) secretion and expression of inducible nitric oxide synthase (iNOS). Significant induction of pro-inflammatory

cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)-α] was evident upon stimulation of murine macrophages, as well as peripheral blood mononuclear cells (PBMCs) isolated from patients with active TB disease, with rRv2626c. Stimulation with rRv2626c also enhanced the expression of costimulatory molecules such as B7-1, B7-2 and CD40 on murine macrophages. We further show that the production of NO and pro-inflammatory cytokines in response to rRv2626c is mediated by the transcription factor nuclear factor (NF)-κB, and this was further confirmed using pyrrolidine dithiocarbamate (PDTC), a specific pharmacological inhibitor of NF-κB. Rv2626c therefore appears to modulate macrophage effector functions by eliciting both innate and adaptive immune responses, suggesting its possible use as a vaccine candidate.

Table S1 Results from multiple linear regression fitting age and

Table S1. Results from multiple linear regression fitting age and cytomegalovirus (CMV) status as co-variates. Table shows the unstandardized coefficient, significance and 95% confidence interval from the output of SPSS software for each CD45RA/CD27 subset. Unit of age is equal to 1 year. Table S2. Mean frequencies and the standard error of the mean of CD40 ligand (CD40L), interferon-γ (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-α (TNF-α) in all possible combinations in each CD45RA/CD27 subset. “
“Hereditary angioedema (HAE) is a rare disease characterized by episodes of potentially

life-threatening angioedema. For affected children in the United Kingdom, there are relatively few data regarding disease prevalence, service organization and the humanistic burden of the disease. Dabrafenib concentration To improve knowledge in these areas, we surveyed major providers of care for children with HAE. A questionnaire was sent to major paediatric centres to determine patient numbers, symptoms, diagnostic

difficulties, Olaparib concentration management and available services. In addition, all patients at a single centre were given a questionnaire to determine the experiences of children and their families. Sixteen of 28 centres responded, caring for a total of 111 UK children. Seven children had experienced life-threatening crises. One-third of patients were on long-term prophylactic medication, including C1 inhibitor prophylaxis in four children. Eight centres reported patients who were initially misdiagnosed. Broad differences in management were noted, particularly regarding indications for long-term prophylaxis and treatment monitoring. We also noted substantial variation in the organization of services between centres, including the number of consultants contributing to patient care, Guanylate cyclase 2C the availability of specialist nurses, the availability of home therapy training and the provision of patient information. Ten of 12 patient/carer

questionnaires were returned, identifying three common themes: the need to access specialist knowledge, the importance of home therapy and concerns around the direct effect of angioedema on their life. To our knowledge, this study represents the first dedicated survey of paediatric HAE services in the United Kingdom and provides useful information to inform the optimization of services. “
“Galectin-3, an endogenous glycan-binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. However, the role of galectin-3 within the CD4+CD25+Foxp3+ T regulatory (TREG) cell compartment has not yet been explored. Here, we found, in a model of Leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral TREG cells both in draining lymph nodes (LNs) and sites of infection. These observations correlated with an increased severity of the disease, as shown by increased footpad swelling and parasite burden.

Pre-warmed PBS was slowly inflated into the lungs and withdrawn

Pre-warmed PBS was slowly inflated into the lungs and withdrawn. The pooled sera were then centrifuged, and the supernatants were maintained at −70°C until use for ELISA. The cell pellets were resuspended and washed twice in PBS. The total cell numbers

were counted using a haemocytometer after RBC lysis using ACK lysis buffer (Invitrogen, Carlsbad, CA, USA). The BALF cell smears were prepared using a Cytospin apparatus (Hanil Science industrial Co., Gyeuangku, Inchun, Korea). The smears were then stained with Diff-Quik solution (Dade Diagnostics of Puerto Rico. Inc., Aguada, Puerto Rico) to determine the cell differentials, in accordance with RGFP966 chemical structure conventional Androgen Receptor antagonist morphological criteria. The results were calculated after three consecutive experiments. All animal studies were approved by the Animal Care and Use Committee of Pusan National University. After the mice were killed, the spleen, lung and lung draining lymph nodes were disrupted and treated with ACK hypotonic lysis solution (Sigma-Aldrich) for 2 min at room temperature for RBCs (red blood cells) lysis. After RBC lysis, the remaining cells were filtered with 100 μm mesh (Small Parts, Inc. Miramar, USA), and the cells were plated in 48 well plates as 5 × 106 cells/mL in RPMI 1640 with 10% foetal bovine serum and penicillin/streptomycin. For the CD3 stimulation

experiments, 0·5 μg/mL of CD3 antibody

(BD Pharmingen™, San Diego, CA, USA) was added to cell-plated wells. Plated cells were incubated for 72 h at 37°C in an atmosphere of 5% CO2. Following incubation, the culture media was harvested and stored at −20°C. The quantities of IL-4, IL-5, IL-13, IL-22, IL-17 and IL-17F in the BALF were determined using an enzyme Cobimetinib datasheet immunoassay, as previously described (22). Mouse lung epithelial cells (MLE12) were obtained from the American Type Culture Collection. Primary lung epithelial cells were isolated from C57BL/6 mice as described previously (22,24), after depletion with anti-CD32/CD16 and anti-CD45 antibodies (Miltenyi Biotec, Bergisch Gladbach, Germany). The cells were then treated with 0·01–1 μg/mL ES proteins. After 2 h of stimulation, the cells were collected and lysed, and the total RNA was extracted. Mouse embryonic fibroblast (MEF) cells were isolated from wild-type (WT) mouse, toll-interleukin 1 receptor (TIR) domain-containing adapter-inducing interferon-β (TRIF) knock out (KO), and Myeloid differentiation primary response gene (MyD) 88/TIR-domain-containing adaptor protein (TIRAP) KO C57BL/6 mouse foetuses 10 days after fertilization. Total RNA extracted using TRIzol reagent (Invitrogen Life Technologies, Milan, Italy) was used to generate cDNA using oligo-dT, random hexamers and SuperScript RT II (Invitrogen, Carlsbad, CA, USA).

Case Report: A 56-year-old man was referred for investigation of

Case Report: A 56-year-old man was referred for investigation of see more nocturnal polydipsia and an elevated serum creatinine of 130 μmol/L. The patient’s history included GORD, hypertension and

gout. The patient had no history of kidney disease or drug allergies. The patient’s medications consisted of Allopurinol 300 mg daily, Verapamil 180 mg daily, Meclobomide 600 mg daily and Perindopril 7.5 mg nocte. He had also been taking Omeprazole 20 mg mane for four years. PPI-induced AIN was suspected and the patient’s serum creatinine normalised to 80 μmol/L following the replacement of Omeprazole with Ranitidine 300 mg daily. The serum creatinine deteriorated to 175 μmol/L after the Omeprazole was reintroduced because of worsening symptoms of GORD but returned to 80 μmol/L after the Omeprazole was again replaced with Ranitidine. Six months later, whilst taking Ranitidine 300 mg daily,

the serum creatinine unexpectedly deteriorated to 195 μmol/L and the patient developed a normochromic normocytic anaemia and sterile pyuria. A kidney biopsy confirmed a diagnosis of AIN. The Ranitidine was ceased and a four-week course of prednisolone was instituted. Four years later, the serum creatinine was 90 μmol/L. Deteriorating symptoms of GORD and concern regarding worsening oesophagitis prompted a trial of Famotidine 20 mg nocte. The serum creatinine promptly increased to 180 μmol/L and normalised following withdrawal of the Famotidine. Conclusions: As far as we are aware, this Trametinib supplier is the first reported case of AIN to

both PPIs and H2RAs in a patient. 279 GRAM NEGATIVE SEPSIS POST RENAL TRANSPLANT BIOPSY IN PATIENT WITH ASYMPTOMATIC PYELONEPHRITIS H AL-KHAYYAT, N TOUSSAINT, S HOLT, P HUGHES Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia Background: Pyelonephritis in patients post renal transplantation Tacrolimus (FK506) has a reported incidence between 10–25% and nearly half of cases are asymptomatic. Transplant pyelonephritis shares many histopathological changes with cellular rejection (interstitial infiltrate, tubulitis) and may mask detection of rejection. Case Report: 41-year male with end-stage kidney disease secondary to IgA nephropathy (haemodialysis for 6 years) underwent a cadaveric renal transplant in 2004. Other medical history included hypertension, ischemic heart disease, and AF on warfarin. With worsening graft function after 10 years (Cr increased from 140 to 200 μmol/L) a renal biopsy was performed. The patient was asymptomatic and admitted the day before as he was rurally based. Pre-biopsy tests included urine microscopy which was pending at the time of the procedure.

At present in Darwin, Australia, patients on substantial immunosu

At present in Darwin, Australia, patients on substantial immunosuppressive therapy, such as adults on

Forskolin solubility dmso 40 mg/day or more of prednisolone or equivalent corticosteroid therapy for 4 weeks or more and those on severe chemotherapy, are recommended for TMP + SMX 160 mg/800 mg (one double strength tablet) daily during the monsoonal wet season. While the value of recommendations for preventing exposure to B. pseudomallei has not been formally evaluated, such recommendations are seen as increasingly important with the escalating numbers of patients in endemic areas with diabetes, chronic renal disease and heavy immunosuppressive therapy. Most important is limiting exposure to wet season soils and surface water in these patients by avoiding gardening or other risk activities during the wet season, or as a minimum wearing protective foot-wear and protective gear during such activities. With the increasing concern of potential inhalation of B. pseudomallei, high-risk patients are now being told to stay indoors during severe

weather events where Buparlisib molecular weight winds and rain may result in B. pseudomallei contaminated droplets or aerosols.[55] Successful management of melioidosis requires a high index of suspicion for early diagnosis, adequate prognostic evaluation of its severity and specific anti-microbial therapy for a prolonged duration to avoid mortality. Melioidosis could potentially be avoided with adequate preventive measures. Hence, the overall need for awareness of this potentially fatal infectious disease among physicians managing at-risk patients cannot be underestimated. None declared. “
“Increasing evidence implicates 5FU psychosocial factors including depression, anxiety, perceived social support

and health-related quality of life in the pathophysiology of various chronic diseases. Research examining the psychosocial aspects of kidney disease has focussed predominantly on depressive disorders in dialysis patients where they are independently associated with increased risk of mortality and poor health-related quality of life. In contrast, studies examining the influence of psychosocial factors in people with chronic kidney disease (CKD) prior to the initiation of renal replacement therapy are sparse. Limited data indicate that clinical depression and depressive symptoms are common and may independently predict progression to dialysis, hospitalization and death. In contrast, the influence of anxiety disorders, lower perceived social support and impaired health-related quality of life on the clinical course of CKD have received little attention. Large-scale prospective cohort studies are needed to clarify the burden and prognostic impact of these factors in this vulnerable population. Given the escalating burden of CKD worldwide examining the role of these potentially modifiable risk factors is crucial.

At the systemic level, serum IgA peaked around 3 weeks post-infec

At the systemic level, serum IgA peaked around 3 weeks post-infection (WPI) and decreased thereafter (Figure 3). Serum IgG quickly increased to a asymptote around three WPI and remained consistently high throughout the infection (Figure 3). Changes in serum IgA and IgG were significantly different between treatment

(infected and controls) and the interaction between treatment and WPI, MI-503 datasheet when the analysis was corrected for the random effect of the host and the nonindependence of sampling the same individual over time (Table 4). Mucus IgA and IgG patterns exhibited similar trends: values were significantly higher in the infected, compared to controls, and decreased from section 1 to section 4 of the small intestine; mucus IgG also increased with sampling time in infected rabbits (Table 4). Graphidium strigosum: Infected rabbits mounted a strong somatic IgA and IgG response at the systemic level but the local antibody response was relatively low to both adult and L3 stages (Figures 4 and S2).

Specifically, serum IgA and IgG significantly differed between treatments and increased with infection time in infected individuals (Table 5). Mucus IgA and IgG were higher in the infected compared to the controls, and Tigecycline in vivo for the infected, values increased with the course of infection showing stronger response in the fundus compared to the antrum section of the stomach (Table 5). Together these findings suggest that rabbits develop an effective systemic and local antibody response to T. retortaeformis but an inefficient mucosal response to G. strigosum. Trichostrongylus Phosphoglycerate kinase retortaeformis: Total white blood cell

and lymphocyte counts were significantly higher in infected hosts compared to the controls and consistently increased over the course of the infection (Figure 5). No significant trend was recorded for eosinophils and neutrophils, corrected for the random effect of the host and the dependence of sampling the same individual over time (Figure 5). However, a more detailed analysis showed that during the second-to-fifth WPI, coinciding with the peak in antibody response, a strong eosinophilia, anaemia (haemoglobin) and high total white blood cells were recorded in infected compared to control rabbits (Table 6). Graphidium strigosum: A consistent increase in the concentration of eosinophils, lymphocytes, total white blood cells and haemoglobin was observed with the progression of the experiment but no significant differences were recorded between the infected and the controls (Figure 6, Table 6). In line with T. retortaeformis infection high eosinophilia, neutrophilia and total white blood cell concentrations were found during the second-to-the fourth WPI in infected compared to the controls; no significant development of anaemia was observed during this infection.

albicans isolate was interpreted as susceptible-dose dependent (S

albicans isolate was interpreted as susceptible-dose dependent (S-DD) and two C. tropicalis isolates were interpreted as resistant IWR-1 price with BMD. On Etest-RPG, trailing growth caused widespread microcolonies within the inhibition zone and resulted in confusion in MIC determination. On Etest-GMB, because of the nearly absence of microcolonies within the zone of inhibition, MICs were evaluated more easily. We conclude

that, for the determination of fluconazole MICs of trailing Candida isolates, the Etest method has an advantage over BMD and can be used along with this reference method. Moreover, GMB appears more beneficial than RPG for the fluconazole Etest. “
“Accurate and fast yeast identification is important when treating patients with invasive fungal disease as susceptibility to antifungal agents is highly species related. Matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF-MS) provides a powerful tool with a clear potential to improve current diagnostic practice. Two MALDI-TOF-MS-systems (BioTyper/Bruker and Saramis/AXIMA) were evaluated using: (i) A collection of 102 archived, well characterised

yeast isolates representing 14 different species and (ii) Prospectively collected isolates obtained from clinical samples at two participating laboratories. Of the 102 archived isolates, 81 (79%) and 92 (90%) were correctly identified by Saramis/AXIMA and BioTyper/Bruker respectively. Saramis/AXIMA was unable to separate Candida albicans, C. africana and C. dubliniensis in 13 of 32 isolates. After manual interpretation of the mass spectra output, all 13 isolates were correctly identified, resulting in an Hydroxychloroquine nmr overall identification performance of 92%. No misidentifications occurred with the two systems. Of the routine isolates one laboratory identified 99/99 (100%) and 90/99 (91%) to species level by Saramis/Axima and conventional

identification, respectively, whereas the other laboratory identified 83/98 (85%) to species level by both BioTyper/Bruker and conventional identification. Both MALDI-TOF-MS Histamine H2 receptor systems are fast, have built-in databases that cover the majority of clinically relevant Candida species, and have an accuracy that outperforms our conventional identification systems. “
“Although the therapeutic efficacy of antifungals is well known for dermatophytosis in general population, limited data exist for patients with chronic kidney disease. The objectives of this study were to determine the dermatophyte species causing infection in patients with end-stage renal disease (ESRD) and in vitro susceptibility of isolated dermatophytes to antifungals. A total of 87 patients with ESRD who undergoing haemodialysis and 105 patients with normal renal function suspected with dermatophytosis were included. Skin scrapings or nail clippings were examined by direct microscopy and cultured on Sabouraud agar. In vitro antifungal susceptibility tests were performed using a broth microdilution method.

Previously, polyfunctional T cells producing IFN-γ, TNF-α and IL-

Previously, polyfunctional T cells producing IFN-γ, TNF-α and IL-2 have been suggested find more as possible markers of protective immunity, based on observations that vaccine-induced triple positive T cells correlated well with protection 18–24. However, other studies reported that such T cells were associated with active TB disease 25–28. The nature of Mtb DosR antigen-responsive CD4+ and CD8+ T-cell subsets in untreated Mtb-exposed donors who had been infected several decades ago, yet never developed any signs or symptoms of active TB (ltLTBIs), was studied here. In vitro purified protein derivative of Mtb (PPD) negative (PPD−) donors were included as uninfected controls. PBMCs of ltLTBIs and PPD−

donors were stimulated with Mtb DosR-regulon-encoded antigens or corresponding peptide pools and the responses were analyzed using multi-parameter flow cytometry (Supporting Information Fig. S1A and S1B). Donors were considered positive when the frequency of a double or poly learn more functional T-cell subset population was ≥0.2%, which is equivalent to ≥200 events. In ltLTBIs high percentages of IFN-γ, TNF-α and/or IL-2 cytokine-producing CD4+ and CD8+ T cells were found in response to PPD (0.23–7.91% and 0.25–7.55%, respectively), Rv2031c protein (0.21–19.71% and 0.25–20.35%, respectively) and the

Rv2031c peptide pool (0.2–16.28% and 0.23–32.92%, respectively), whereas no such responses were observed in PPD− controls (Fig. 1A). The highest frequencies were consistently found within the single cytokine-producing CD4+ and CD8+ T-cell populations. Interestingly, many double producing T cells were identified within the CD8+ T-cell population, as shown by Fig. 1B, which depicts the proportions of polyfunctional as well as double and single cytokine-producing T cells. For Mtb DosR antigen Rv1733c, two peptide pools

were tested (Fig. 1C). Again high CD4+ and CD8+ T-cell responses were observed (0.43–14.41% and 0.2–14.25%, respectively), with single positive cells being the most frequent. In addition, substantial numbers of double cytokine-producing CD4+ and CD8+ T cells were present in both peptide pool responsive CD4+ and CD8+ T-cell populations, IFN-γ+TNF-α+ CD8+ T cells being the most frequent (Fig. 1D). Low to no Rv1733c-specific responses were identified within the PPD− controls (Fig. 1C). Miconazole A comparable pattern was observed for Rv2029c (0.29–8.41% CD4+ T cells and 0.36–9.55% CD8+ T cells). Unlike Rv1733c, the Rv2029c protein induced a considerable fraction of IFN-γ+TNF-α+ CD8+ T cells. Some responses to Rv2029c peptide pool 1 were also observed in the PPD− group, but no responses were seen to peptide pools 2 and 3 (Fig. 1E and F). Of note, stimulation of PBMCs with Staphylococcus enterotoxin B induced high percentages of CD4+ and CD8+ T cells producing single (0.3–26.44% CD4+ T cells and 0.29–12.6% CD8+ T cells), double (0.23–22.26% CD4+ T cells and 0.

Cumulatively, these data therefore suggest that the inability to

Cumulatively, these data therefore suggest that the inability to respond to IL-6 is not a direct consequence of T-bet expression by Treg cells.

Exposure to retinoic acid (RA) promotes resistance to IL-17 production in nTreg via down-regulation of CD126 expression [[17]]. RA is produced at sites of inflammation [[18]] and whether such an effect in the inflamed CNS might maintain the IL-6-insensitive phenotype of CNS T cells is worthy of further investigation. Recent fate-mapping studies showed that the majority of CD4+ effector T cells infiltrating the CNS during EAE have, at some point, produced IL-17 [[19, 20]]. Unlike their Foxp3− counterparts however, CNS-derived Foxp3+ cells showed no history of IL-17 expression [[20]]. We can therefore conclude that the KU-60019 cost inflammatory environment within the CNS fails to induce IL-17 production by the infiltrating Foxp3+ T cells and, from our data here, that these cells resist conversion, even when experimentally Enzalutamide concentration challenged under potent IL-17-inducing conditions that work on Treg cells taken from noninflamed sites. Besides inducing IL-17 production in Treg

cells, several inflammatory cytokines, including IL-6, can also render effector T cells resistant to suppression as measured using in vitro assays [[5, 21]]. On this point, our data on the insensitivity of CNS GFP− cells to IL-6 are noteworthy, and would exclude such a function of IL-6 within the CNS, at least one that acted directly on T cells. We demonstrate that the response of CNS-Treg cells to inflammatory cytokines cannot

be predicted accurately from the behavior of peripheral Treg cells taken from the same individual. This has implications for human studies that sample Treg cells from the circulation, such as the recent description of elevated IFN-γ production by peripheral blood Foxp3+ cells from multiple sclerosis (MS) patients [[22]]. The prediction from our study would be that CNS-Treg cells in MS might maintain suppressive, rather than effector function. Furthermore, concerns that Treg cells that have been manipulated therapeutically might develop unwanted effector function (based on in vitro observation using “naïve” Treg cells) might be overstated. Perhaps the most interesting MG-132 molecular weight feature of our current comparison of CNS and peripheral T cells is the apparent loss of gp130 from all CD4+ cells in the CNS, given that gp130 is the signaling unit for other cytokines, including IL-11, IL-27, and leukemia inhibitory factor (reviewed in [[7]]). The down-regulation of gp130 should render CNS T cells insensitive to the effects of these cytokines also. Spatial and temporal variation in the expression of cytokine receptors therefore offers a fundamental means of controlling effector and Treg-cell function at different stages of an inflammatory immune response. This possibility certainly warrants further study. Foxp3-GFP mice [[23]] and Foxp3.