These results confirm the observations made by Nemazee and colleagues, who showed that receptor editing in the spleen is marginal and that IgD-positive T2 cells undergo apoptosis upon BCR cross-linking 36. Collectively, our results suggest that BAFF-R expression is regulated by BCR signaling and that the outcome of BCR signaling on BAFF-R expression is B-cell developmental stage dependent, namely a down-modulation on immature B cells

and up-regulation on mature B cells. Recently, SRT1720 we could show that expression of BAFF-R on mature B cells is required for their maintenance and not only for their development beyond transitional type 1 B cells 20. This suggests that for survival, mature B cells do not

rely on surface expression of BCR alone 37. As already mentioned, triggering of both receptors mediates activation of NF-κB, suggesting a potential and elegant mechanism for B cells to determine their lifespan also within the mature compartment. Up-regulation of BAFF-R upon BCR ligation could ensure only on mature B cells an increased survival and allow them to undergo the necessary final differentiation stages within the B-cell follicles. Findings in support of this assumption come from the observations made in mice lacking both Rac-1 and Rac-2. Such mice have defective BCR signaling, resulting in diminished numbers of splenic B cells, but normal numbers of BM B cells. Furthermore, this impaired BCR signaling also leads to reduced levels of BAFF-R, pointing to a direct regulation of BAFF-R expression by BCR signaling via the Rac-1 and Rac-2 pathway 38. Collectively, we suggest a mechanism MLN2238 solubility dmso by which BAFF-BAFF-R signaling determines the survival Grape seed extract time window for B cells beyond the immature B-cell stage, and in particular upon rearrangement and expression of their BCR. The tight control of surface BAFF-R expression by BCR ligation according to the developmental stage supports our hypothesis. Thus, B cells can exploit the same signaling mechanisms for two different outcomes according to the biological requirements, namely reduced survival/deletion of auto-reactive B cells

within immature B cells and increased survival within mature B cells. In addition, our data allowed us to link mouse and human B-cell biology in regard to BAFF-R expression. In both species, BAFF-R expression starts at the immature B-cell stage and a correlation exists between BAFF-R and surface IgM expression, suggesting that for human B cells as well, the BCR is controlling BAFF-R up-regulation. Moreover, we show that recombination, by means of RAG2 expression, is almost exclusively confined to the BAFF-R negative fraction. Thus, for immature B cells in the mouse, BAFF-R expression is induced on positively selected cells. Female C57BL/6 mice were purchased from RCC (Füllinsdorf). Mice were used at 6–8 weeks of age.

Fibrinolysis is an important defence mechanism against thrombosis, but has only been studied locally in BP and no systemic data are available. The aim of this observational study was to evaluate systemic fibrinolysis and coagulation activation in patients with BP. We measured parameters of fibrinolysis and coagulation by immunoenzymatic methods in plasma from 20 patients with BP in an active phase and during remission after

corticosteroid treatment. The controls were 20 age- and sex-matched healthy subjects. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1) antigen, PAI-1 activity and tissue plasminogen activator (t-PA) antigen were significantly higher in the BP patients with active disease than in healthy controls (P = 0·0001 for all), as were the plasma levels of the fibrin fragment d-dimer and prothrombin fragment

F1+2 (P = 0·0001 for both). During remission after treatment, levels of PAI-1 www.selleckchem.com/products/gdc-0068.html antigen and PAI-1 activity decreased significantly (P = 0·008 and P = 0·006, respectively), and there was also a significant decrease in plasma levels of d-dimer (P = 0·0001) and F1+2 (P = 0·0001). Fibrinolysis is inhibited in patients with active BP, due mainly to an increase in plasma levels of PAI-1. Corticosteroids not only induce the regression of BP lesions, but also reduce the inhibition of fibrinolysis, which may contribute Olaparib research buy to decreasing thrombotic risk. Bullous pemphigoid (BP) is an autoimmune blistering disease that occurs typically in the elderly [1] and is burdened with a high risk of death, due mainly to sepsis and cardiovascular events [2]. It involves the skin and rarely the mucous membranes, and is characterized by the presence of blisters usually surrounded by erythematous–oedematous lesions. The diagnosis is supported by histology showing

a subepidermal blister with a dermal mixed inflammatory cell infiltrate usually rich in eosinophils, and a direct immunofluorescence examination of perilesional skin revealing the linear deposition of immunoglobulin (Ig)G and/or C3 in the basement membrane zone (BMZ). Circulating MRIP anti-BMZ autoantibodies can be detected by means of an enzyme-linked immunosorbent assay (ELISA) for two hemidesmosomal antigens, BP180 and BP230 [3, 4]. Autoantibodies against these antigens play an important role in the pathogenesis of BP, as well as complement activation and leucocyte infiltration [1, 5]. Inflammatory cells (particularly autoreactive T cells and eosinophils) participate in blister formation by producing and releasing a number of cytokines and soluble factors that amplify and maintain tissue damage [6-8]. The inflammatory response induces an activation of blood coagulation which is involved both locally, by amplifying the inflammatory network in lesional skin, and systemically, by leading to a prothrombotic state [4, 9-12].

[44-48] Whenever it is available and affordable lipid AmB formulations are the standard in the therapy of mucormycosis, and if initiated early enough, it can significantly decrease dissemination and mortality.[49, 50] Isavuconazole, a recently developed azole, does have activity against Mucorales

in vitro and in vivo[51, 52] and is a promising antifungal agent. Drug efficacy is often compromised by the lack of selective fungicidal activity to fungi but also by the evolution of drug resistance, which could potentially arise after prolonged exposure of fungal organisms to agents with fungistatic effects. Recently, a DNA analysis of R. oryzae showed that its genome was highly repetitive containing 2 to 10-fold duplication events relative to A. fumigatus genome in gene families related to fungal cell membrane and cell wall synthesis.[24] Selleckchem Kinase Inhibitor Library Atezolizumab Such over-representation of the specific gene families could explain the poor efficacy of antifungal agents against R. oryzae.[53] In the absence of new drugs in the market, there is a growing need for implementing new antifungal strategies to enhance antifungal drug efficacy against Mucorales. The appropriate use of combinatorial schemes, including drug-to-drug or drug-to-host interactions, aim to simultaneously inhibit

multiple pathways and thus enhance antifungal potency, decrease emergence of resistance, reduce drug toxicity and block fungal viability. Up to date, clinical findings on combination antifungal therapy for mucormycosis are limited and come primarily from uncontrolled retrospective case studies and compassionate-use programs. Nevertheless, observational clinical data offer encouragement that combination therapy strategies may improve the outcomes of patients with mucormycosis. In addition

to 3-mercaptopyruvate sulfurtransferase the findings of in vitro and preclinical studies related to the efficacy of antifungal combinations as well as the effects of immune host defence against various Mucorales species under the influence of antifungal agents, the potential combination strategies conducted in retrospective open label clinical studies and the respective outcomes have been reviewed elsewhere.[54, 55] Terbinafine (TER), an “old” antifungal agent, which inhibits sterol biosynthesis, exhibits low MICs against Mucorales and has been used to treat patients with invasive mucormycosis.[56] An early in vitro antifungal combination study, investigating the interactions of AmB with TER and rifampin (RIF) as well as those of VRC with TER against 35 isolates of Mucorales showed synergy between AmB and TER for 20% of the strains, while the interaction between AmB and RIF exhibited synergy or additivity depending on the Mucorales species. Additionally, the combination of VRC with TER showed synergistic interactions for 40% of the isolates with significant differences between genera.[57] The efficacy of PSC in the presence of CAS or AmB was also shown to have synergistic effects against Mucorales.

Louis, MO, USA).

Microtiter plates (Nunc Immunoplates) coated with TcSP recombinant protein (2 μg/mL) or epimastigotes lysate (5 μg/mL) in carbonate buffer (pH 9·6) were incubated overnight at 4°C. The plates were washed with PBS containing 0·05% Tween 20 (PBST) and then incubated with blocking buffer (PBS containing 5% skim milk) for 1 h at 37°C. Mouse polyclonal sera were diluted (1 : 50) in blocking buffer, added to duplicate series of wells and incubated for 1 h at 37°C. Wells were washed six times with PBST, incubated with 50 μL of biotinylated anti-mouse immunoglobulin (IgG1, IgG3, GSK458 mw IgG2a and IgG2b) antibodies (Zymed) at a dilution of 1 : 1000 in PBST and incubated for 2 h at room temperature. The plates were washed five times with PBST and incubated with 50 μL of a 1 : 1000 dilution of horseradish peroxidase-streptavidin (Zymed) for 1 h at 37°C. The plates were washed as described and then developed with 2,2-azino-bis[3-ethylbenzthiazoline]-6-sulphonic acid (Zymed). The coloration was developed for 20 min at room temperature. Absorbance was determined at 405 nm in an ELISA reader (Labsystem Multiskan MS, Helsinki, Finland). Cytokines were analysed in serum collected 14 days after the last immunization using a Flow Cytomix Mouse Th1/Th2 10plex kit, a set of fluorescent beads for quantitative

detection of cytokines in serum according learn more to the manufacturer’s instructions (BMS820FF; Bender MedSystems, Vienna, Austria). Briefly, serum samples in assay buffer and beads coated with specific antibodies were incubated to allow for a reaction against cytokines and specific anti-cytokine biotinylated antibodies, followed by washing and centrifugation.

The samples were incubated with conjugated streptavidin-phycoerythrin and analysed in a FACScalibur Flow Cytometer (BD Biosciences, San Jose, CA, USA). Cytokine concentrations were resolved using the Flow CytomixPro Software (Bender MedSystems). The results are expressed as means ± SD. Statistical analysis was performed using one-way selleck anova followed by a Bonferroni post hoc test to identify significantly different groups. The survival time was calculated by the Kaplan–Meier method with Mantel-Cox log-rank test. Differences were considered to be statistically significant when the P-value was  < 0·05. Screening of a T. cruzi genomic expression library with anti-TcSSP4 (T. cruzi amastigote-specific surface protein 4) antibodies revealed 10 highly positives clones [28], one of which (A83) was selected for further characterization. This clone encodes a surface protein of the TS superfamily (TcSP) (data not shown) and contains three domains: A (N-terminal), R (central amino acid repeats sequence) and C (C-terminal). Initial experiments revealed that the recombinant protein rTcSP was recognized by sera from the T. cruzi-infected mice (see below), indicating that the native protein is immunogenic.

Conflict of interest: The authors declare no financial or commercial conflict

of interest. See accompanying Commentary: http://dx.doi.org/10.1002/eji.201040447 “
“Epigenetic control of gene expression is critical for cellular differentiation and development. Macrophage development, polarization and activation are also controlled by DNA and histone modifications. This Viewpoint summarizes the recent findings on https://www.selleckchem.com/Caspase.html the role of histone modifications regulating macrophage polarization toward M1 and M2 subtypes. Macrophages play pleiotropic roles in responding to various stresses such as infection, genotoxic stress and injury 1. Furthermore, macrophages are critical for tissue remodeling and angiogenesis in the late stages of inflammation, tumor progression and metabolic homeostasis. Macrophages develop from hematopoietic stem cells through common myeloid progenitors in the BM, and repopulate in peripheral tissues 2. Currently, macrophages can be classified into several different subtypes, based on their reactions to different stimuli 3–5. Macrophages involved in inflammatory responses to bacterial and viral infection are called M1 macrophages. M1 macrophages produce high

amounts of NVP-LDE225 purchase proinflammatory cytokines, such as TNF, upon recognition of invading pathogens

by a set of pattern-recognition receptors including TLRs, GPX6 RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs) 6–8. M1 macrophages are known to produce nitric oxide (NO) by expressing inducible NO synthase (iNOS) and are critical for clearing bacterial, viral and fungal infections. IFN-γ produced by activated T cells and TLR ligands, induces M1 macrophage generation in vitro. On the other hand, macrophages involved in responses to parasite infection, tissue remodeling, angiogenesis and tumor progression are called “alternatively activated macrophages” or “M2 macrophages” 3. M2 macrophages are characterized by their high expression of markers of alternative activation, including arginase-1 (Arg1), chitinase-like Ym1 (Chi3l3), found in inflammatory zone 1 (Fizz1), mannose receptor (MR), chemokines such as CCL17, CCD24 and so on 9–13. The pattern-recognition receptor system responsible for the recognition of helminth infection and M2 polarization has yet to be identified; however, stimulation of macrophages with the Th2 cytokines IL-4 or IL-13 induces M2-type macrophages 4, 14. In addition, immune complex formation, IL-10 and glucocorticoid or secosteroid hormones are also known to generate M2 macrophages.

caninum antigens

were not indicative for protection (10,41,45). this website Assessment of i.n. vaccinated animals confirmed the earlier findings on the protection achieved with recNcPDI (19). Of course, one problem with i.n. vaccination is the restricted amount of antigen which can be administered to mice. Nevertheless, i.n vaccination of mice with the 1 μg recNcPDI antigen conferred protection against cerebral disease (90%), together with low cerebral parasite burden. Association of recNcPDI with the chitosan/alginate or chitosan/alginate-mannose nanogels may have increased this efficacy – with the antigen associated with chitosan/alginate nanogels, 100% of the mice were protected – however, the high number of protected mice with the antigen in the absence of nanogels precluded a clear indication that the nanogels had an added value. It would be necessary to perform additional studies, in which the antigen load per vaccination was titrated, to see whether the limit of inducing protective antibody is lower with nanogel-associated antigen. Nevertheless, the present work demonstrates that nanogel-associated antigen is indeed an efficacious vaccine, and the results from the i.p. vaccination suggest that the nanogels are providing an

added value to the vaccine efficacy. Moreover, quantification of cerebral infection intensities in i.n. vaccinated animals showed that nanogel delivery of the vaccine had an advantage over the nanogel-free vaccine. Although the chitosan/alginate nanogel-associated antigen appeared to be more efficacious than chitosan/alginate-mannose Ulixertinib nanogel-associated antigen in limiting cerebral infection compared, the differences were only slight. Others have shown that protective immune responses against experimentally induced neosporosis in acute disease mouse models have been mainly associated with the development of a Th1-type immune response, dominated by IgG2a antibody production and natural killer (NK) cell proliferation with increased IFN-γ production enough (51,52).

However, there are also reports on protective effects achieved by Th2-type responses in acute disease (40,42–44) and in foetal infection models (44). All these observations support the idea that both Th1 and Th2-driven immune mechanisms can limit disease, at least in the mouse model. Indeed, our own results are showing the presence of a mixed Th1/Th2 response induced in nanogel-delivered vaccine immunized mice, protected from disease, and showing reduced cerebral parasite load. To elaborate on the type of immune response (Th1 or Th2) induced, we analysed the level of cytokine mRNA transcription in splenic tissue. It is important to note that the cytokine pattern described is the combined result of immune responses to both vaccination and infection.

The immunomodulatory properties of the selected Lactobacillus bacteria were assessed by measuring the induction of innate and adaptive cytokine production, proliferation and cell death of unstimulated, polyclonal stimulated and allergen-specific stimulated hPBMC. The Lactobacillus strains studied showed an overall stimulating effect on IL-10, decreased prototypical Th2 cytokines and differentially stimulated signature Th1 cytokine induction. Blood was collected from five birch pollen-allergic patients, two grass pollen-allergic patients

and one adult healthy control. All birch- and grass-allergic patients reported having rhinoconjunctivitis during the birch or grass pollen season, respectively, and had serum-specific IgE to birch

or grass pollen Trichostatin A datasheet of at least class 4 (except for one person who had class 3), measured by ImmunoCAP Vincristine supplier (Phadia AB, Uppsala, Sweden). The healthy donor displayed no birch or grass pollen-specific IgE in his sera (<0.35 kU L−1/class 0). Blood was obtained outside the pollen season in September, and none of the patients showed allergic symptoms at the time of investigation. Furthermore, none of the patients had received allergen-specific immunotherapy or used antihistamines or corticosteroids in the month before the blood drawing. All participants gave their informed consent and the performed experiments were approved by the local ethical committee (Commissie Mensgebonden Onderzoek, regio Wageningen). Six Lactobacillus strains (Table 1) of the species Lactobacillus acidophilus, Lactobacillus plantarum and Lactobacillus fermentum were selected from our culture collection on the basis of high survival rates under conditions of low pH and/or the presence of bile, isolation from gastrointestinal tract, or were strains from species that are among the predominant Lactobacillus populations in the human gut. Further selection, including 70 strains, was based on IL-10-inducing capacities in 24-h hPBMC cultures of a healthy donor according to standardized procedures in our laboratories. Furthermore,

a mixture of strains B2261 and B633 was included, further referred to as a mixture of B2261 and B633. The choice for this mixture was based on combining the highest IL-10-inducing strain (B633) and the highest Thalidomide IL-12-inducing strain (B2261), of the 70 strains included in this initial screening. Strains were cultured for 24 h at 37 °C in Man Rogosa Sharpe (MRS) broth (Merck, Darmstadt, Germany), after which fresh broth was inoculated with 1% (v/v) overnight culture. After an additional 24 h of incubation at 37 °C, bacterial cells were harvested by centrifugation at 1000 g, washed twice with phosphate-buffered saline (PBS), and resuspended in PBS. The bacterial cell numbers were determined by plate counting on MRS agar, and OD was measured at a wavelength of 600 nm.

Then, cultures were pulsed with 1 μCi/mL (methyl-3H)thymidine (New England Nuclear) for the last 18 h. Results are expressed as cpm ± SD of triplicate determinations. A total of 60 μg of PEI with or without 8 μg of poly A:U (PEI-PAU) was incubated 30 min to form the complexes. B16 melanoma cell line was stimulated with PEI

or PEI-PAU for 4 h, washed three times with PBS, and incubated for additional 20 h with complete medium. B16 cells were washed and melanomas were established in C57BL/6, TLR3−/−, and IFNAR1−/− mice by subcutaneous injection of 1 × 106 cells into the right flank. Tumor development was monitored every day as described previously (18). To evaluate the therapeutic activity of PEI and PEI-PAU, C57BL/6 and TLR3−/− mice were inoculated with 1 × 106 B16 cells. Once tumors reached approximately 5 mm3, they were treated intratumorally with PEI (40 μg/200 μL) or with PEI-PAU (40 and 50 μg, respectively, Compound Library cell assay in 200 μL) five times for every 2 days. Statistical analysis was done using the Tukey post test to ANOVA analysis with the InfoStat software (National University of Córdoba). Values of p < 0.05 were considered significant. This work was supported by grants from SECyT-UNC, ANPCYT-PICT 2007–0974, Instituto Nacional del Cancer 2011 (INC-MSAL); CONICET 2008–6437, Fundación Fiorini and Roxadustat datasheet Fundación para el Progreso de la Medicina. G.G. is a postdoctoral

fellow from CONICET. N.G.N. and D.A.N. are PhD fellows from CONICET and FONCyT, respectively. M.M. is member of the Researcher Career of CONICET. The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, Methisazone but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Figure S1. PAU-B16 CM partially reverse the inhibitory effect of B16 cell-derived factors on CpG-mediated BMDC maturation. Figure S2. IFNβ produced by poly I:C-activated

tumor cells can mature DC and reverse the suppressive effect of cancer cell-derived factors on R848-mediated MoDC maturation. Figure S3. IFNβ produced from poly I:C-treated tumor cells synergizes with TLR ligand to promote T cell proliferation in a MLR assay. “
“Up to one in four lung-transplanted patients develop pulmonary infiltrates and impaired oxygenation within the first days after lung transplantation. Known as primary graft dysfunction (PGD), this condition increases mortality significantly. Complex interactions between donor lung and recipient immune system are the suspected cause. We took an integrative, systems-level approach by first exploring whether the recipient’s immune response to PGD includes the development of long-lasting autoreactivity.

Antibody–antigen complex was separated by precipitation with 20% Protein A Sepharose (Invitrogen) and washed eight times (ELx50 Microplate Strip Washer, Biotek,

Winooski, VT, USA). Antibody-bound radioactivity PS-341 was analysed in a Beta-counter. The Sepharose-bound radioactivity was converted into arbitrary units (U) using individual standard curves of T1D sera with high ZnT8Ab reactivity. The experiments were conducted in duplicate wells and in two independent experiments. In an identical assay as described above, sera and different concentrations (pmol/l) of the long cold in vitro translation ZnT8R and ZnT8W (aa 268–369) proteins were incubated with radiolabelled ZnT8R or ZnT8W (aa 268–369) proteins in the competitive RBA. The experiments were conducted in duplicate wells and in three independent experiments. Displacement experiments were carried out in three different independent experiments using duplicate determinations. The mean and standard error of the mean (SEM) were calculated for these three independent experiments. Affinity was calculated as half-maximal (Kd) and maximal (Vmax) binding and expressed as pmol/l. Affinity differences between the R and W proteins were tested with two-tailed

paired t-test. P-value <0.05 was considered to be statistically significant. The purity of the short ZnT8 peptides after high performance liquid chromatography (HPLC) and analysis by MS was 70% (data not shown). Silmitasertib clinical trial Each one of the three peptides, ZnT8R (533.60 m/z), ZnT8W (543.60 m/z) and ZnT8Q (524.26 m/z) had a mass that corresponded to the expected monoisotopic mass. The degree of purity was reflected by 6–10 minor components, each representing a not immediately obvious contamination (data not shown). All 12 BALB/c mice immunized with the three short ZnT8 (318–331) peptides developed varying levels of peptide antibodies as detected by ELISA (data not shown). Two mice from each group with the highest titer after immunization with one of the three ZnT8 (318–331) peptide variants (R,

W and Q, respectively) Carnitine palmitoyltransferase II were tested for sequence specificity. All mice failed to develop antibodies able to distinguish the three peptide variants (Fig. 2, panels A-F). The M6-Q mouse showed 1,000-fold higher binding to the ZnT8Q than to the ZnT8R (318–331) peptide, while there was no difference in binding to the ZnT8W peptide (Fig. 2, panel F). These mouse sera were next tested in the ZnT8 Triplemix RBA (Fig. 3). Triplemix ZnT8Ab were observed in 6 of 12 immunized mice. The highest titer was achieved in a W peptide immunized mouse, while the lowest titer was in a mouse immunized with the Q variant. The remaining six mice showed binding that did not differ from blank or a non-immunized mouse. Immunized BALB/c mice showed normal urinary pH, glucose and protein during the immunization period (data not shown).

Members of the TNFRSF play a diverse role in fine-tuning immune responses and several members

are preferentially expressed on Foxp3+ Treg cells including the GITR (TNFRSF18), OX40 (TNFRSF4) [25], and DR3 (TNFRSF25) Etoposide datasheet [26]. One major issue that remains unresolved is whether therapeutic targeting of TNFRSF members can be used to enhance Treg-cell function in vivo and whether this approach can be used as an alternative to IL-2 treatment [27] or Treg-cell cellular biotherapy [28]. Although some studies have demonstrated the selective effect of agonist mAbs or soluble ligands to these receptors on Treg-cell function [13] in the mouse, interpretation of most of these studies is complicated because these reagents also exert potent costimulatory effects on Teff cells and some of the reagents may result in Treg-cell depletion [16]. Some of the latter studies have probably been misinterpreted as demonstrating reversal of Treg-cell suppressor function secondary Dactolisib cost to engagement of the GITR on Treg cells. In order to dissect the role of the GITR in Treg cell/Teff cell function, we have analyzed the effects of GITR stimulation by soluble Fc-GITR-L under a number of experimental conditions. In healthy, unmanipulated mice Fc-GITR-L treatment resulted in a short-term expansion of Treg cells accompanied by a modest enhancement of Tconv cells. In contrast, in the absence of Treg cells, Fc-GITR-L resulted in

marked enhancement of the numbers of Teff cells in the IBD model, but had little effect on their differentiation. In the presence of both Teff and Treg cells in the IBD model, the effects of Fc-GITR-L treatment on Treg cells were much more complex. In the presence of WT Teff cells and WT Treg cells, administration of Fc-GITR-L resulted in a moderate decrease in the numbers of the Treg cells and in their suppressive function. However, when GITR KO Teff cells were cotransferred with WT Treg cells and the recipients treated with Fc-GITR-L, there was a dramatic decrease

in the numbers of Treg cells and a loss of their suppressive Etomidate function. One caveat in the interpretation of the IBD experiments is that they were all performed in immunodeficient mice and both the Teff cells and the Treg cells undergo marked homeostatic proliferation under these conditions. Nevertheless, this experimental protocol allowed us to define specific effects of GITR engagement on both subpopulations and to exclude any effect of GITR-L on cells of the innate immune system. In general, GITR-L treatment augmented the number of IFN-γ-producing cells, but had no effect of the number of IL-17-producing cells. The role of IL-17 in the pathogenesis of IBD remains controversial [29]. In some studies, we have observed an increase in IL-17-producing cells under conditions where Treg cells have had a therapeutic effect. It is possible that these cells represent protective Th17 cells [30].