We found that the surface protein A (SasA) of S. aureus could protect mice from lethal challenge of the bacteria. Staphylococcus aureus, a conditional pathogenic Gram-positive bacterium, is the leading cause of bloodstream, lower respiratory tract and skin/soft-tissue infections, accounting for 20–25% of all nosocomial infections (1,2,3). Bacteremia is the most prevalent type of S. aureus infections in hospitalized patients, followed by lower respiratory tract infections and skin/soft tissue infections (4,5). S. aureus is able

to adapt to new antibiotics and acquire antibiotic resistance (6). The extensive use of antibiotics has resulted in increased resistance among S. aureus clinical isolates. In patients with large area burn, it was found that more than 90% of S. aureus isolates were resistant to 11 types of antibiotics, including ampicillin, cefazolin, ciprofloxacin, gentamicin, levofloxacin, clidamycin, erythromycin, oxacillin, penicillin(16). click here Due to multi-drug resistance and the ability to SAHA HDAC purchase acquire resistance to new antibiotics quickly, it is more and more difficult to treat S. aureus infection, especially with the emergence of vancomycin resistant S. aureus strains (7,8). As a result, many investigators resort to immunological approaches to contain S. aureus infection (9). Many components of S. aureus, such as capsular polysaccharide (9), poly-N-acetylglucosamine

(10), clumping factor A (11), clumping factor B (12), iron-regulated surface determinant (IsdB) (13) and fibronectin-binding protein (FnBP) (14), can generate immune responses that afford partial protection against S. aureus challenge in experiment animals. It is difficult to develop S. aureus vaccines because there are many pathogenic determinants in S. aureus and different clinical isolates may have different pathogenic determinants. Ideal vaccine candidates for S. aureus should be expressed broadly in different S. aureus

clinical isolates and be consistent among different strains. Vaccines consisting of several components may induce better protective immunity against infective Mephenoxalone S. aureus (15). In this study, to screen good vaccine candidates against S. aureus, a panel of pathogenic proteins of S. aureus was expressed and dot blotted with sera from mice infected with S. aureus USA300, 546 and 1884, respectively. The proteins that interact with the sera were selected to immunize BALB/c mice. The immunized mice were then challenged with S. aureus USA300. A protein named SasA was found to be able to induce protective immunity against lethal challenge of S. aureus USA300. Staphylococci were cultured on tryptic soy agar or in broth at 37 °C. S. aureus USA300 were obtained from ATCC. This strain does not produce toxic shock syndrome toxin. The lethal dosage of S. aureus USA300 or S. aureus 546 was determined before as in respectively. S. aureus 546 and S. aureus 1884 were obtained from China Veterinary Culture Collection Center (CVCC). E.

). A band with a molecular weight of about 46 000 with a faint band underneath appeared, which was greatly enhanced when B cells were activated with CD40L + IL-4 (Fig. 1c). AID and A3G mRNA expression were then evaluated by real-time PCR. All results were expressed as mean (± SEM) relative to unstimulated cells, which were accorded an arbitrary value of 100. CD40L induced an increase in AID mRNA from 100 to 258 (± 131) and to a lesser extent in A3G mRNA to 128 (± 13), these failed to reach the 5% level of significance (Table 1). However, IL-4 significantly R788 mw up-regulated AID (P = 0·037) but not A3G (P = 0·29). The combined CD40L + IL-4 B-cell agonists up-regulated significantly both

AID and A3G mRNA (P < 0·05), and this was much greater for AID than A3G mRNA (Table 1). CD40L + HLA class II antibodies (177 ± 25) was more effective for A3G mRNA (P = 0·027) than that for AID mRNA (295 ± 128, P = 0·11). As with immunofluorescence the other B-cell agonists were not pursued further. The results suggest that CD40L + IL-4 www.selleckchem.com/GSK-3.html yielded the most consistent and significant increases in both mRNA and protein of AID and A3G. We have evaluated a major function of AID in B cells by demonstrating a significant

increase in the cell-surface expressions of IgG (P < 0·001) and IgA (P < 0·0001) (Fig. 2b,c) when stimulated with CD40L + HLA-II mAb and to a lesser extent with CD40L + IL-4 (P < 0·03). The IgM also increased but to a greater extent with CD40L + IL-4 than CD40L + HLA-II mAb (Fig. 2a). These studies were then extended to the culture supernatants of the B-cell-agonist-stimulated cells. Using the Luminex bead technology confirmed the increase in IgA antibodies in the 4-day culture supernatants

of CD40L + IL-4-stimulated B cells (Fig. 3). The 6·4-fold higher concentration of IgA compared with IgG1 was surprising as the reverse is normally found Ureohydrolase in serum. This might be related to the shorter half-life of IgA (about 9 days) compared with that of IgG (about 21 days). After 7 days of culture, the supernatants showed a significant increase in IgG4 by stimulation with CD40L + IL-4 (P = 0·01), though the total concentration was moderate (12·6 ± 5·4 ng/ml) (Fig. 3b). A functional effect of up-regulation of A3G by stimulating primary B cells with the selected agonists was studied in HIV-1 (BaL) infectivity of autologous CD4+ T cells. Isolated B cells were stimulated with CD40L + IL-4 or HLA-II mAb for 3 days, followed by co-culturing the B cells with autologous CD4+ T cells (activated with phytohaemagglutinin and IL-2 for 3 days) and infected with serial dilution HIV-1 (BaL) for 9 days. The results showed dose-dependent inhibition of HIV-1 replication with the B cells pre-treated with either of the B-cell agonists, compared with the untreated B cells (Fig. 4a,b).

Magnetic resonance imaging revealed a mass lesion at the pineal gland accompanied by obstructive hydrocephalus. Following surgery, pathological examinations demonstrated a pleomorphic granular cell astrocytoma. The patient has been free from recurrence for 24 months after surgery without adjuvant therapy. The specimen exhibited nuclear and cytoplasmic pleomorphism. The nuclei varied in size, shape and coarseness. Variability was also observed in the eosinophilic granular bodies, Rosenthal fibers and spindle-shaped PKC412 tumor cells. GFAP, S-100 and vimentin were immunohistochemically positive. Reticulin network was absent between the tumor cells, and granular cells with ballooned cytoplasm showing positive staining for PAS. Pleomorphic

granular cell astrocytoma is believed to be a form of astrocytoma originating from the pineal gland. Its clinicopathological features resemble those of pleomorphic xanthoastrocytoma. However, it can be differentiated from the latter by the absence of reticulin fibers, absence of basement membrane between adjacent cells, and presence of large numbers of mitochondria. “
“A. Ekonomou, M. Johnson, R. H. Perry, E. K. Perry, R. N. Kalaria, S. L. Minger and C. G. Ballard (2012) Neuropathology and Applied Neurobiology38, 344–353 Increased neural progenitors in individuals with cerebral small vessel disease Aims:

Recent work has highlighted a significant increase of neural stem/progenitor cells after stroke in humans. In this study, we examined neurogenesis in small vessel disease, a key concurrent pathology Lapatinib purchase in Alzheimer’s disease. Methods: We assayed autopsy tissue from 13 vascular dementia patients with small vessel disease and 12 age-matched subjects without cerebrovascular pathology, undertaking immunohistochemistry in the affected brain area and the subventricular zone with a well-characterized battery of antibodies to detect neural stem cells/progenitors and immature Docetaxel molecular weight neurones, as well as choline acetyltransferase immunoreactivity. Results: We showed significant increases ranging from 33% to 92% (P < 0.05) in neural progenitor cells around the areas of microvascular

pathology and in the subventricular zone in patients with small vessel disease compared to individuals without cerebrovascular changes, even in patients with severe cerebrovascular disease, as defined by neuropathological assessment. Some of the progenitor cells give rise to immature neurones in the affected areas. These alterations were associated with vascular changes, but were unrelated to the cholinergic deficit observed in the cortex and subventricular zone in these patients, in contrast to other dementias examined such as dementia with Lewy bodies. Conclusions: This study provides evidence for neurogenesis in small vessel disease and may have important implications for the development of new therapies for neurodegenerative diseases. “
“A. H. Hainsworth, R. C. Allsopp, A. Jim, J. F. Potter, J. Lowe, C. J. Talbot and R. J.

The basis of its stimulatory function is not well understood but is thought to occur through an as yet unidentified receptor.43 In contrast, many of the studies published to date have focused on its inhibitory function, which occurs by signaling through programmed death-1 (PD-1). B7-H1 shares this receptor with the related B7 family member B7-DC. B7-DC appears to have higher affinity for PD-1 than B7-H1,47 but its expression is much more limited than B7-H1, and is found predominantly on macrophages and DCs following cytokine

induction.48 Like B7-H1, CP-690550 cell line B7-DC exhibits dual inhibitory and stimulatory functions, but its restricted expression to APCs suggests that it primarily affects the priming stage of immune responses.49,50 PD-1 is expressed on activated T cells, B cells, and cells of the myeloid lineage and contains two cytoplasmic signaling domains consisting of an intracellular tyrosine inhibitory motif (ITIM) and an intracellular tyrosine switch motif (ITSM).51In vitro studies have suggested that the ITSM on PD-1 is critical for its inhibitory activity

and acts by recruiting SHP-1 and/or SHP-2 phosphatases which then interfere with CD28 signaling by preventing activation of phosphoinositide 3-kinase (PI3K) activation – a critical enzyme in CD28 signaling.52–54 The ultimate effect of PD-1 ligation on self-reactive T cells can be apoptosis or anergy. This regulatory pathway appears essential, as peripheral tolerance to some MHC class I-restricted self-antigens requires PD-1.55,56 In addition, genetic deletion of PD-1 results in severe autoimmunity click here because of the loss of peripheral tolerance of self-reactive T cells.57,58 Blocking PD-1 accelerated the onset and worsened the severity of both spontaneous and induced autoimmune disease.59,60 Similarly, accumulation of self-reactive T cells occurs when B7-H1 and B7-DC are depleted, resulting in increased susceptibility to induced autoimmune disease.46,61 T-cell exhaustion, a state of gradually acquired unresponsiveness to antigen,

can also occur when PD-1 is chronically ligated by B7-H1, although this phenomenon has only been implicated in the failure to clear infection, and it is not certain whether this occurs in tolerance to self-antigen.62 Finally, B7-H1 has also many recently been recognized to have a novel role in inducing differentiation of Tregs from naïve CD4+ T cells.63,64 There is also evidence that binding of PD-1 to B7-H1 or B7-DC can induce signaling through their intracellular domains, back into the APC; although the biological roles of this reverse signaling are less clear. Tumor cells receiving this signal become resistant to CTL-induced cytolysis, without the requirement for PD-1 signaling into the T cell.65 The signaling mechanism for this remains enigmatic but does require the approximately 30 amino acid, evolutionarily conserved cytoplasmic domain of B7-H1. Reverse signaling appears to occur through B7-DC as well.

This small subset of CVID patients have defects in inducible co-stimulator (ICOS), CD19, CD20, CD21, CD81, lipopolysaccharide-responsive beige-like anchor (LRBA), B cell-activating factor (BAFF) receptor and CXCR4 [the latter causing WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome] [3]. Additionally, two autosomal dominant defects affecting the genes for NFκB2 and PIK3CD have been described

recently. The NFκB2 mutation causes haploinsufficiency and results in a CVID-like phenotype with childhood onset, autoimmune features and adrenal insufficiency [4]. Nuclear factor kappa B2 (NF-κB2) is the principal downstream effector in the non-canonical NF-κB pathway and is required for appropriate B cell development.

Dominant gain-of-function mutations in Palbociclib manufacturer the PIK3CD gene encoding the catalytic P110δ and the p85α subunits of phosphoinositide 3-kinase (PI3 kinase) causes hyperactive PI3 kinase signalling, leading to early-onset autoimmunity, recurrent viral infections and bronchiectasis [5, 6]. This suggests that clinical trials with PI3 kinase inhibitors are warranted. Most recently, selleck kinase inhibitor a CVID-like syndrome, characterized by hypogammaglobulinaemia, a progressive loss of circulating B cells, immune dysregulation and lymphocytic infiltration of the brain, lung and gut was recognized to be caused by heterozygous mutations in the CTLA4 gene [7]. CVID patients can be divided into those who exclusively experience infections (bacterial, viral or opportunistic) and, as a result, often develop chronic

lung disease, and a second group who in addition develop an inflammatory condition. In the former subset, where recurrent infections are the primary symptom of concern, affected patients will have a near-normal life expectancy provided that they receive adequate treatment with intravenous immunoglobulin (IVIg) and/or mafosfamide antibiotics. Patients in the inflammatory subset are extremely prone to develop granulomas, autoimmune conditions and malignancies. Granulomas can develop in multiple locations, including the skin, lungs, liver and gut. Autoimmune conditions such as colitis, cytopaenia, hepatitis and malignancies, including leukaemia, lymphoma and colon cancer, are relatively frequent [1]. This subset will generally have a reduced life expectancy and lower quality of life. Additionally, there is a third group encompassing conditions which are not considered ‘classic’ CVID: these are defects in T cell development, resulting in a ‘CVID-like’ condition with early-onset bronchiectasis, autoimmune disease and recurrent viral infections.

IgA1 HR has up to 6 of the 9 potential O-glycosylation sites occupied; some Gal-deficient glycans consist of terminal N-acetylgalactosamine (GalNAc). IgA1 HR O-glycosylation was reported

to be initiated by GalNAc-T2. However, the expression of GalNAc-T2 does not differ between cells from patients and those from healthy controls (HC). In contrast, expression of GalNAc-T14, the enzyme with highest similarity to GalNAc-T2, is 5-fold greater in IgA1-producing cells derived from IgAN patients than in those from HC. Here, we analyzed kinetics and site-specificities of GalNAc-T2 and -T14 on HR using high-resolution mass spectrometry (MS). Methods: We produced recombinant soluble GalNAc-T2 and -T14 enzymes. A synthetic HR peptide (sHR) and a panel of synthetic Selleckchem JQ1 HR glycopeptides (sGP) with a single GalNAc residue at different sites were used as acceptors.

Results: GalNAc-T2 showed higher activity i.e., faster rate of glycosylation of sHR, than did GalNAc-T14. Up to 8 sites were glycosylated in sHR by GalNAc-T2, whereas GalNAc-T14 added GalNAc to up to 5 sites in HR of IgA1. Distinct sHR O-glycoforms generated by GalNAc-T2 and -T14 were subjected to tandem MS to localize glycosylated sites. The sites of glycosylation on sHR catalyzed by GalNAc-T2 and -T14 were the same for the variants with up to 5 sites and BGB324 order appeared predominantly in an ordered fashion: GalNAc was attached to T7 first and then to T15, followed by S11 and T4. Localization of GalNAc on sGP did not affect kinetics of the GalNAc-T2. GalNAc-T14 effectively glycosylated sGP variant with a GalNAc at S9, the site that corresponds to S230 on IgA1 HR, the dominant site with terminal GalNAc in Gd-IgA1 proteins. GalNAc-T2 and -T14 have similar site-specificity on IgA1 HR, but differ in kinetics and how they are affected by preexisting glycosylation. Conclusion: Elevated

expression of a specific GalNAc-T is a possible mechanism Gemcitabine order for production of Gd-IgA1 in IgAN. TAKAHASHI KAZUO1,2, RASKA MILAN1,3, STEWART TYLER J.1, STUCHLOVA HORYNOVA MILADA1,3, VRABLIKOVA ALENA1,3, HALL STACY D.1, HIKI YOSHIYUKI4, YUZAWA YUKIO2, MOLDOVEANU ZINA1, JULIAN BRUCE A.1, RENFROW MATTHEW B.1, NOVAK JAN1 1University of Alabama at Birmingham; 2Fujita Health University School of Medicine; 3Palacky University in Olomouc; 4Fujita Health University School of Health Sciences Introduction: Patients with IgAN have elevated serum levels of galactose (Gal)-deficient IgA1; some hinge-region (HR) O-glycans consist of terminal N-acetylgalactosamine (GalNAc) with or without N-acetylneuraminic acid (NeuAc, sialic acid). Sialylation of GalNAc blocks subsequent galactosylation. IgA1-producing cells from IgAN patients have increased activity of α2,6-sialyltransferase (ST6GalNAc) that sialylates GalNAc.

Plasma-based IWR-1 solubility dmso diagnostics have revolutionized many facets of medicine, as exemplified by the use of troponins for the early diagnosis of acute myocardial infarction. On the other hand, plasma biomarkers may be confounded by extra-renal sources as well as

by subclinical changes in renal elimination. Thus, in the case of AKI, it is important and ideal to develop both urinary and plasma biomarkers. The majority of NGAL results described in the literature have been obtained using research-based ELISA assays that are currently available from commercial sources such as Bioporto (Gentofte, Denmark) and R&D Systems (Minneapolis, MN, USA). These assays are accurate, but are not practical in the clinical

setting. In these regards, a major advance has been the development of a point-of-care kit for the clinical measurement of plasma NGAL (Triage® NGAL Device, Biosite Incorporated, San Diego, CA, USA). In children undergoing cardiac surgery, the increase in plasma NGAL levels measured by the Triage® Device at various time points after cardiopulmonary bypass was proportional to the severity of AKI.66 In terms of diagnostic accuracy, the 2 h plasma NGAL measurement showed an AUC of 0.96, sensitivity of 0.84, and specificity of 0.94 for prediction of AKI using a cut-off value of 150 ng/mL.66 Several addition publications have now confirmed the utility and accuracy of the Triage® NGAL Device in critically ill adults.35–37,55,57 The assay is facile with quantitative click here results available in 15 min, requires only microlitre quantities of whole blood Meloxicam or plasma, and is currently being tested in multicentre trials for further validation. In addition, a urine NGAL immunoassay has been developed for a standardized clinical platform (ARCHITECT® analyzer, Abbott Diagnostics, Abbott Park, IL, USA). In children undergoing cardiac surgery, the increase in urine NGAL levels determined by ARCHITECT® analyzer at various time points after cardiopulmonary bypass was

also proportional to the severity of AKI.67 The 2 h urine NGAL showed an AUC of 0.95, sensitivity of 0.79, and specificity of 0.92 for prediction of AKI using a cut-off value of 150 mg/mL.67 This assay is also easy to perform with no manual pretreatment steps, a first result available within 35 min, and requires only 150 µL of urine. This assay is also currently undergoing multicentre validation in several clinical populations. The genesis and sources of plasma and urinary NGAL following AKI require further clarification. Although plasma NGAL is freely filtered by the glomerulus, it is largely reabsorbed in the proximal tubules by efficient megalin-dependent endocytosis.20 Direct evidence for this notion is derived from systemic injection of labelled NGAL, which becomes enriched in the proximal tubule but does not appear in the urine in animals.

In vitro stimulation of Th2 cells by PGD2 requires much higher concentrations to stimulate IL-10 production compared with IL-4, IL-5 and IL-13.[22, 1] We therefore examined the effect of Pyl A on the Th2-type anti-inflammatory cytokines in the myometrium (Fig. 8). Although no changes in levels of IL-4 were detected, an

increase (non-significant) in IL-5 was observed (Fig. 8). Moreover, a non-significant increase in IL-10 mRNA and protein with LPS and Pyl A treatment was detected consistent with improved protection against LPS-induced fetal loss in mice[65] as well as the reduced rate of naturally occurring fetal loss in IL-10-deficient mice.[24] Although Pyl A led to a small increase in the pro-labour transcription factor NF-κB and the pro-inflammatory cytokines, we did not see an increase in COX-2 protein expression. We therefore examined the direct effect of Pyl A on myometrial contractility ex vivo. Contrary to the expected NVP-BKM120 manufacturer uterotonic effect, Pyl A administration resulted in complete inhibition of circular muscle contractility (Fig. 9), but had no effect on longitudinal

muscle. There is limited knowledge on the functional role of the individual muscle layers of the mouse uterus, the inner circular and outer longitudinal muscle, in pregnancy and parturition. In the myometrium of other species such as the pig and rat, it has been suggested that the function of the longitudinal muscle is to move luminal contents by contraction[66] and that tonic contraction of the circular muscle may be required for spacing and retention of embryos/fetuses.[67] Circular muscle cells have a higher spontaneous selleckchem electrical activity than longitudinal muscle cells during rat pregnancy,[68] and weak high-frequency

contractions in the circular muscle layer prevent movement of fetuses not towards the cervix during pregnancy,[69] supporting its potential role in the maintenance of pregnancy. If circular muscle contraction is necessary for retention of uterine contents, this would explain how inhibition of circular muscle contraction by Pyl A leads to preterm expulsion of the fetuses, as seen in this study. Consistent with this, relaxation of uterine tone is also believed to be important during human labour.[70] It is proposed that relaxation of the lower segment of the uterus, in conjunction with contractions of the fundal region, is required for the passage of the fetus through the birth canal. Alternatively, relaxation of circular muscle may not be important in murine labour. Many rodent studies suggest that by term, the function of circular muscle becomes more similar to the longitudinal layer, and that contractility of both the circular and longitudinal muscle is required for labour.[71-74] It is possible that despite the inhibitory effect on contractions seen with Pyl A ex vivo, that the overwhelming in vivo inflammatory effect was enough to overcome the tocolytic effect resulting in preterm labour.

002). By the rectal route, specific antibodies measured after immunization increased, but less than by the subcutaneous route, and not significantly (P=1.06); the mean OD405 nm is 0.9. Whatever the route of immunization (rectal, intragastric and subcutaneous), the antibody titres were highly variable between animals in the same group. The SDs were very high. After challenge, the median survival times were highly variable within groups. The challenge outcome in all groups is presented in Fig. 2. The three immunization

routes were significantly different from each other (P=0.05). There click here was no correlation between serum anti-Cwp84 titres and postchallenge survival. Animals immunized by the subcutaneous route had the highest antibody level, but Neratinib concentration only 17% of them (1/6) survived to the C. difficile challenge on day 11. Fifty percent of hamsters (3/6) immunized by the rectal route survived to C. difficile challenge. The group immunized by the intragastric route did not seem to be protected against the challenge; no hamsters from this group survived on day 11. As the animal challenge results observed for the rectal route were promising, we decided to perform a second assay, under exactly the same conditions, but increasing the number of animals and including the analysis of the faecal pellet samples in order to monitor the colonization and to analyse

the results observed in the protection

assay. For this survival study, groups were composed, respectively, of 18 animals for the immunized group and 16 animals for old the control group. The challenge outcome in the control group and the group immunized by Cwp84 is presented in Fig. 3. Postchallenge survival was significantly prolonged in animals immunized with Cwp84 as compared with the control group (P=0.038). Within the first 5 days, 90% of hamsters from the control group died (15 out of 16 animals died). Among the animals immunized by Cwp84, 33% survived the challenge (six out of 18 animals survived). Signs of morbidity such as inactivity and wet tail or diarrhoea were not always apparent before dying. After the C. difficile challenge, the numbers of viable C. difficile bacteria (vegetative cells and spores) present in faecal samples were determined every day during 1 week in order to examine C. difficile intestinal colonization. There were differences in colonization onset among hamsters. Challenge of hamsters with the 79-685 C. difficile strain resulted in colonization of 90% of the control group; each colonized animal developed infection leading to death, which was observed from day 2 to day 6. In the immunized group, the colonization reached 66% (Fig. 4). For the two groups, 1 day after challenge, C. difficile was not detected in any sample. Onset of colonization was variable, ranging from 1 to 5 days after challenge.

Normal mice and IL-17a−/− mice that received antibody to IL-22 had more rapid bacterial dissemination outside of the lungs [30]. Therefore, we considered that IFN-γ and IL-22 mediated protective immune response to M. tuberculosis. In the present study, soluble IL-17 could not be detected in pleural fluid from patients with TBP. The low levels of IL-17 in patients with TBP might be because of the inhibition of Th1 conditions at the site of disease. Murine studies demonstrated that IFN-γ limited the Th17 lineage formation in vitro [31, 32]. IL-17 in bronchoalveolar lavage fluid and pleural fluid from most subjects,

even Everolimus order in the absence of inhibitory Th1 cytokines, was too low to be directly detected by ELISA [33–35]. Other studies showed that in patients with neutrophilic airway inflammation following exposure to organic dust, IL-17 level of bronchoalveolar lavage fluid was also undetectable,

except in those with the most severe inflammation [36]. However, the IL-17 expression by PFMC at both mRNA and protein levels was increased by stimulation with dominant peptides of ESAT-6, CFP-10 or BCG in vitro. This indicated that M. tuberculosis-specific Th17 cells were present at the local site of disease, but pathogen-related factors hampered the ability of the Th17 cells to provide protective immune response. Hence, it was likely that the immune response to M. tuberculosis Wnt tumor infection was much more complicated in vivo than which was revealed by in vitro stimulation. The mechanisms in this process would be the focus of future studies. Our findings of ESAT-6-, CFP-10- or BCG-specific Th1, Th22 and Th17 cells in tubercular pleural fluid were consistent with studies from Scriba et al. [42]. They found the presence of two mycobacterium-specific CD4+ T cell populations in peripheral blood of persons exposed to or diseased by M. tuberculosis. The presence of these M. tuberculosis-specific T cells in pleural fluid might be because of the selective recruitment of specific cells

to the site of infection. This would be consistent with previous studies, which suggested that low Th1 frequencies at the periphery might result from T cells homing to the site of infection [37–39]. We found selleck chemical that IL-22 and IL-17 were produced mainly by CD4+ T cells, which was consistent with results from Khader et al. [19] and in contrast to data from a murine model that showed that after mycobacterium infection, γδ T cells were the main source of IL-17 in the lungs [40]. We demonstrated that ESAT-6-, CFP-10- or BCG-specific Th22 and Th17 cells were distinct from each other and from Th1 cells. This was consistent with our previous study showing that IL-22-producing CD4+ T cells specific for Candida albicans were different from Th1, Th2 and Th17 cell subsets [41]. Thomas et al.