In this way, T cell assays may provide immune surrogate marker(s)

In this way, T cell assays may provide immune surrogate marker(s) of clinical efficacy and provide evidence that the treatment had impacted upon the subject’s immune system. This would confirm that the route and dose chosen was sufficient to stimulate changes in immune function. Importantly, if the trial did not identify an effective therapy, knowledge of changes

in T cell function, or the failure to induce them, would guide the development of future therapeutic approaches. see more The ideal T cell assay would require a small amount of blood (<5 ml), be technically very simple, have very low intra- and inter-assay variability, be specific for the appropriate islet antigens, work equally well with fresh and cryopreserved peripheral blood mononuclear cells (PBMCs) and give a quantitative measure of islet antigen-specific effector and regulatory T cell responses. Although this ideal may not become a reality, this list highlights the technical challenges to be overcome if an informative assay is

to be developed. None the less, an assay that achieved some, if not all, the criteria listed above would still be very useful. What has prevented the development of T cell assays for islet antigen-specific Talazoparib mw T cell responses? The major problem is that the frequency of islet antigen-specific T cells is very low in the blood. The frequency of proinsulin76–90-specific CD4+ T cells has been estimated to be ∼1 in 300 000 [21]. The frequency of flu matrix 58–66-specific CD8+ T cells has been estimated to be ∼1 in 200 cells [22], and the frequency of self-reactive proINS- (proINS34–42, proINS101–109) or GAD65 (GAD65536–545, GAD65114–123)-specific CD8+ T cells has been assessed on ∼1 in 1000 cells and ∼1 in 2500 cells, respectively [23–25] (and James and Durinovic-Belló, unpublished observation). In almost all cases, peripheral venous blood is the only tissue available for routine analysis in humans. Another hurdle is that autoreactive T cells are

not only rare but are also of low functional avidity, making it more difficult to detect them. This feature stems from the fact that most high-avidity autoreactive T cells are deleted in the thymus, so that the repertoire of T cells reaching find more periphery becomes skewed towards lower-avidity T cell receptors. The third challenge is to determine which antigens are the targets of the pathogenic autoimmune response and hence the most appropriate for stimulating T cell responses in vitro. Several formats of antigen have been used. Brooks-Worrell et al. [26] have used protein extracts from human islets, separated by electrophoresis and transferred to nitrocellulose, to measure T cell responses. The use of islet protein extracts avoids the need to choose a single protein or epitope.

Experimental evidence showed that antibodies targeting the high-a

Experimental evidence showed that antibodies targeting the high-affinity iron permease, an iron transporter cell membrane protein, protect DKA mice from infection with R.

oryzae infection.[37] DAPT order Moreover, antibodies targeting the GRP78/CotH interactions (i.e. antiGrp78 antibodies[43] or antiCotH antibodies[47]) protected DKA mice from infection with R. oryzae. These findings lend support for the future development of novel passive immunisation strategies that target virulence traits of Mucorales. Mucormycosis is a lethal infection with very limited and mainly ineffective treatment options. Although considered rare, mucormycosis are on the rise and this increase is expected to continue due to the increased number of immunosuppressed patients and the severity in the immunosuppression regimens. Additionally, the increased cases of obesity and unhealthy life style will increase cases of diabetes, which are uniquely predisposed to mucormycosis. Clinical data point to the importance of iron acquisition in the pathogenesis of mucormycosis and subsequent research confirmed this observation. Although mucormycosis pathogenesis studies are at its infancy, recent major discoveries highlight the possibility of translating this knowledge into possible novel therapies urgently needed to improve the outcome of this disease.

This work was supported in part by Public Health Service grant R01 AI063503. The author received research grants or consultancy fees from the following companies to conduct Selleck MAPK inhibitor research on mucormycosis: Astellas, Enzon, Gilead, Merck and Pfizer. “
“Summary Aspergillus fumigatus is currently the major airborne fungal pathogen that menaces immunocompromised individuals. Germination Flavopiridol (Alvocidib) of inhaled conidia is a hallmark of the early infection process, but little is known about the underlying mechanisms. The intention of our ongoing studies is the identification of A. fumigatus

proteins that are differentially expressed during germination and may provide insights in the germination process. Using a proteomic approach, we identified AFUA_5G09330 as a major hyphal-specific protein. This result was confirmed using monoclonal antibodies generated in this study. AFUA_5G09330 belongs to a fungal-specific protein family. The eponymous CipC protein of A. nidulans has been shown to be induced by concanamycin A, and transcriptional data from Cryptococcus neoformans demonstrate a strong up-regulation of the expression of a homologous gene during infection. Our data provide evidence that AFUA_5G09330 is a monomeric, cytoplasmic protein. We found no evidence for an overexpression of AFUA_5G09330 induced by concanamycin A or other stress conditions. AFUA_5G09330 is exclusively found in the hyphal morphotype that enables an invasive growth of A. fumigatus during infection.

At 46 days of age, the chickens in each group were challenged i v

At 46 days of age, the chickens in each group were challenged i.v. with 0.5 mL of a bacterial suspension containing 108 CFU/mL of E. coli O78 strain J46, which harbors the iss, tsh cvaC, and papC genes. Z-VAD-FMK clinical trial The LD50 value of this challenge strain for i.v. infection against 5-week-old chickens is 2.9 × 107 CFU /bird. The challenged chickens were observed for 7 days, and their clinical signs scored as follows: none = 0, reluctance to walk = 1, mild depression or ataxia = 2, depression or astasia = 3, death = 4. Dead chickens were necropsied immediately on the day of death. Seven days after challenge exposure, the surviving chickens

were killed and necropsied. Macroscopic lesions were recorded and scored separately for each organ as follows: heart and pericardium (normal = 0, turbid with excessive or cloudy fluid in the pericardial cavity or partial pericarditis = 1, marked pericarditis = 2, severe pericarditis or death = 3); liver (normal = 0, small amount of fibrinous exudate = 1, marked perihepatitis = 2, severe perihepatitis or death = 3). Samples for bacteriologic examination were taken from the liver and heart of each chicken at necropsy. Twenty 19-day-old embryonated eggs

were allotted to two equal groups and immunized with AESN1331 or sterile PBS. Each egg was oriented with ICG-001 supplier the large end up and a hole punched in its top with an 18-gauge needle. Using a 21-gauge needle, an inoculum of 10 μL (103 CFU) of AESN1331 per egg (or an equivalent volume of PBS) was injected into the amniotic fluid. All inoculated eggs were then hatched in the same incubator. Hatching was assessed after 21.5 days of incubation. Until exposure to challenge, the hatched chickens were monitored daily for signs of illness and for death. At 28 days of age, all chickens were challenged and assessed as described above. Fisher’s exact test was used to compare the number of dead chickens and the number of organs positive for the challenge Casein kinase 1 strain in each group. Student’s two-tailed t-test was employed to compare the clinical and the lesion scores between experimental groups. A P value of < 0.05 was considered significant. We compared the in

vitro and in vivo properties of the mutant strain to those of the parent; results are summarized in Table 1. As with the parent, E. coli O78 antiserum agglutinated AESN1331. Colonies of the mutant were smaller than those of the parent. AESN1331 colonies were colorless on MacConkey agar, demonstrating an inability to ferment lactose. AESN1331 also was unable to ferment D-mannose, D-sorbitol, L-rhamnose, sucrose and D-melibiose, but could still ferment glucose and L-arabinose. Although the mutant had lost tryptophan deaminase activity and indole production, the strain resembled its parent in harboring β-galactosidase, lysine decarboxylase, ornithine decarboxylase, and oxidase activities while lacking arginine dihydrolase, citrate production, H2S production, urease, acetoin production, gelatinase, and ability to reduce NO3− to NO2−.

[62-65] Our results suggest that RBV enhances the TAA-specific ce

[62-65] Our results suggest that RBV enhances the TAA-specific cellular immune response in association with down-modulation of Treg-cell activity. As previously reported for CPA,[66] this hypothesis may contribute to preventing the progression

to hepatocellular carcinoma in patients with HCV infection who were successfully treated with IFN plus RBV. To confirm this hypothesis, long-term observation of patients receiving pegylated IFN plus RBV therapy will be needed. In addition, it must be determined whether continuous Y-27632 in vitro administration of RBV after the elimination of HCV can contribute to the prevention of hepatocellular carcinoma. In this report, we demonstrated the ability of RBV to inhibit the differentiation of naive CD4+ T cells into CD25+ FOXP3+ Tregadapt cells through the inhibition of Treg1-type regulatory cells. Although the mechanism of action by which RBV regulates Treg cells is not fully understood, we expect that these findings will contribute to establishing a new approach

for regulating immune responses in patients with various diseases caused by immunological impairment. We are grateful to Dr Taku Tsukui, Division of Gastroenterology, Department of Medicine, Nippon Medical School, Tokyo, Japan, for critical reading of this manuscript and helpful suggestions. The authors declare that there is no conflict of interest. “
“Aeromonas have been isolated from a wide variety of aquatic environments.

However the number of Aeromonas in sea water is extremely small compared to that in fresh water. In in vitro culture, Aeromonas can grow in mediums containing B-Raf inhibition NaCl at a concentration of 3.0%, this concentration corresponding Acyl CoA dehydrogenase to that of sea water. It is unclear why the number of Aeromonas is low in sea water. Exoproteins of bacteria are thought to be important for bacterial growth and survival in the environment. Previously, the present authors have shown that mediums containing 3.0% NaCl suppress production of two proteases, serine protease and metalloprotease. In this experiment, other exoproteins whose production is influenced by the amount of NaCl in the medium were analyzed. A protein whose production is repressed in medium containing 3.0% NaCl was found and purified. Biological assay of the purified protein showed that it degrades tributyrin and hydrolyzes para-nitrophenyl-fatty acylesters. These results show that the protein is a lipase. Subsequently, the nucleotide sequence of the gene encoding the lipase was determined and the amount of mRNA of the lipase gene in the cells measured. It was found that transcription of the gene is not inhibited by NaCl in the medium. This result indicates that the lipase might be synthesized, but the folding process to become an active structure does not progress smoothly in a medium containing 3.0% NaCl. Motile Aeromonas spp. (A. sobria, A. hydrophila, and A.

These tasks are fulfilled by Treg cells and so-called tissue sign

These tasks are fulfilled by Treg cells and so-called tissue signaling leukocytes, respectively (reviewed in [43]). In addition, the specificity of bystander Th cells is still unclear, but it seems at least in allergen-specific eczema a substantial proportion, in particular of Th17 cells, is specific for staphylococcal antigens [12, 29] rather than for the eliciting allergen [8, 36]. Furthermore, increasing evidence exists that Th cells recognizing autoantigens may differentiate during the immune reactions in atopic eczema [44], lupus

erythematosis [45], or psoriasis [46]. It can be hypothesized that these autoreactive Th cells migrate into the tissue as bystander cells, encounter their antigen and serve as amplifiers find more of inflammation. In summary, recruitment of antigen-specific Th cells into tissues initiates a cascade of immune events in the skin that is mediated by the majority of bystander T cells that in parallel migrate to the site of inflammation. Once a Th cell reaches its target organ and

is fully activated, it exerts its function via cell contact dependent mechanisms as well as secretion Barasertib in vivo of soluble mediators such as chemokines and cytokines. Roughly, T-cell functions in inflamed tissue are (i) inflammation aimed at clearing the potentially harmful antigen, (ii) limitation of the immune response to prevent a cytokine storm with massive collateral tissue damage, and (iii) regeneration of tissue homeostasis after inflammation. Importantly, all three functional arms have to be in homeostasis,

as imbalance of any of these may have negative outcomes (Fig. 2). A simplified view to functionally categorize Th cells would be that IFN-γ-, TNF-α-, and IL-17-producing subtypes are mainly inflammatory, IL-10- and TGF-β-producing T cells are mainly limiting, Rolziracetam and IL-22 secretion is mainly associated with coordinating regeneration (Fig. 1). However, most cytokines have overlapping functions and are not exclusively attributable to the aforementioned functions. Furthermore, the function of a single cytokine critically depends on the context of the local microenvironment. Much progress has been made in understanding T-cell functions in a disease-specific context. This can be exemplified by three model diseases: psoriasis, atopic eczema and ACD that will be discussed separately in the following section. The pathogenesis of psoriasis is dominated by the Th17 cytokines IL-17, IL-21, IL-22, and TNF-α [30, 47-50]. IL-17 and IL-22 [51] as well as IL-22 and TNF-α [4, 52] co-operatively induce the secretion of antimicrobial peptides by epithelial cells such as human beta defensin 2 and S100 proteins, which prevent microbial colonization. Overrepresentation of IL-22 turns its positive role in tissue regeneration into a pathologic one through the induction of acanthosis, or thickening of the skin [53]. IL-21 has been shown to co-operate with IFN-γ in inducing epidermal hyperplasia [54].

4) This response

was further enhanced by the addition of

4). This response

was further enhanced by the addition of IFN-α, as both the R2+ and the R2− AM14 B cells proliferated even more robustly. These results show that FcγRIIB normally downregulates the response to RNA-associated IC both in the absence and in the presence of IFNα, and in its absence, buy Galunisertib B cells can now respond to these common autoantigens. In this study, we have used both spontaneous and defined IC to examine the role of FcγRIIB in the activation of autoreactive B cells. PL2-3 (anti-histone) and BWR4 (anti-RNA) are both IgG2a mAb isolated from autoimmune-prone mice, and when added to primary B cells in culture, they bind to undefined DNA-/RNA-associated components of cell debris to form IC. These PL2-3 and BWR4 IC activate AM14 B cells through mechanisms that are TLR9 and TLR7 dependent, respectively. However, our previous studies have shown that the AM14 response to BWR4 and other RNA-associated IC is markedly enhanced by Alectinib purchase the addition of type I IFN 18. These effects

presumably reflect the capacity of type I IFN to dramatically increase the level of TLR7 expression in B cells 30 and lower the BCR signaling threshold 14. We also found that type I IFN enhanced the response to defined CG-poor dsDNA IC, although it appeared to induce only a minimal increase in the level of TLR9 expression 14. We now show that FcγRIIB deficiency eliminates the need for exogenously supplied type I IFN in both the response to BWR4 and the CG-poor dsDNA. Therefore, quite remarkably either the addition of type I IFN or the loss of FcγRIIB can convert nonstimulatory or weak stimulatory autoantigen to a potent activator of autoreactive B cells. It follows that the activation of B cells with low-affinity receptors for self-antigen reflects the integration N-acetylglucosamine-1-phosphate transferase of signals of variable strength

emanating from both activating (BCR, TLR7/TLR9 and IFN receptor) and inhibitory (FcγRIIB) receptors. A certain final signal strength must be achieved in order for the B cells to cross a proliferation “threshold”, and this threshold can be attained by either increasing the affinity of the TLR-derived signal or recalibrating the BCR signaling cascade. A relatively weak (IgG2a) FcγRIIB ligand is sufficient to limit the response to weak TLR signals (CG-poor dsDNA fragment IC or BWR4). The mechanisms responsible for crosstalk between surface receptors (BCR, FcγRIIB and IFNAR) and endosomal receptors (TLR7, TLR9) remain to be fully elucidated. It has been well established that FcγRIIB blocks ITAM-dependent BCR signaling through recruitment of the phosphatase SHIP and dephosphorylation of key molecules involved in the BCR signaling cascade 31. In addition, common molecules activated by both the BCR and the TLR signaling pathways could be targets for FcγRIIB inhibition.

However, the prevalence

of subtler forms of neurocognitiv

However, the prevalence

of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we ABT-263 research buy have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients.

The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. Methods: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. Results: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. Conclusion: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease. “
“Ependymosarcoma CHIR-99021 clinical trial is a new entity of Idoxuridine malignant gliomas composed of ependymal and sarcomatous components. We report a rare case of ependymosarcoma

with eosinophlic cells which occurred to the right trigon of the lateral ventricle. A 62-year-old man complained of headaches over a 2-month period. A hard, gray mass was found in the right trigon of the lateral ventricle during the operation. Although he received radiation and chemotherapy, the patient died due to tumor disseminating through the whole brain within 7 months after the operation. The histological examination revealed that the anaplastic glial components intermingled with the sarcomatous components. Immunohistochemically, sarcomatous cells were positive for α smooth muscle actin and desmin. However, anaplastic glial cells were not positive for these markers. In addition, Masson trichrome stain showed a plethora of collagen fibers between sarcomatous cells, but no collagen fibers were produced by the glial tumor cells. Solid focal papillary lesions of the glial tumor showed dot-like epithelial membrane antigen and diffuse cytoplasmic D2-40 immunoreactivity. Based on the above findings, these anaplastic glial tumor cells should show focal ependymal differentiation, and sarcomatous cells show myofibroblastic differentiation.

Taken together, we conclude that CTLA-4-Ig affects the level of c

Taken together, we conclude that CTLA-4-Ig affects the level of cytokines and chemokines in the affected tissue by significantly reducing IL-4, IL-1β, MIP-2 and IP-10. To analyse the effect of CTLA-4-Ig on systemic inflammation, serum samples taken 24 and 48 h after challenge were analysed by ELISA for the acute-phase proteins

SAP and haptoglobin. These factors have been shown to be reliable Tamoxifen order markers of inflammation in this model as their serum levels correspond to ear swelling (A.D.C. and C.H., data not shown). Furthermore, increased serum concentration of these components indicates systemic inflammation with involvement of the liver [18]. Figure 6b,d shows that serum levels of SAP and haptoglobin were reduced significantly following treatment with CTLA-4-Ig compared to control treatment at both 24 and 48 h after challenge in the DNFB-induced model, and in the oxazolone-induced Barasertib concentration model serum concentrations of haptoglobin were suppressed significantly after both 24 and 48 h (Fig. 6c). Similarly, SAP was reduced significantly after 48 h but not at 24 h (Fig. 6a). Based on these findings, we conclude that CTLA-4-Ig inhibits systemic inflammation as measured by circulating levels of SAP and haptoglobin. In the CHS model, it is not known whether CTLA-4-Ig exerts its effect in the sensitization

phase alone or whether the presence of CTLA-4-Ig is also important in the effector phase. To test this, we set up an adoptive Montelukast Sodium transfer system in which donor mice were sensitized in the presence or absence of CTLA-4-Ig. After 5 days, cells from the draining lymph node were transferred to recipient mice which had been treated with CTLA-4-Ig 24 h earlier or left untreated. Recipient mice were subsequently challenged with DNFB and ear swelling was measured 24, 48 and 72 h after challenge. As shown in Fig. 7, mice transferred

with cells exposed to CTLA-4-Ig during both the sensitization phase and the challenge phase or during the sensitization phase alone (labelled +/+ and +/−, respectively) exhibited a significantly suppressed ear-swelling response compared to the untreated control group (labelled −/−). In contrast, the mice which were treated only with CTLA-4-Ig during the challenge phase (labelled −/+) exhibited ear swelling similar to the untreated mice. Taken together, these results indicate that CTLA-4-Ig exerts its immunosuppressive effect primarily during the sensitization phase. We next tested whether regulation of cytokines and chemokines in the inflamed tissue followed the same pattern as ear swelling by comparing levels of IL-1β, IL-4, IP-10 and MIP-2 in the adoptive transfer model treated with CTLA-4-Ig in the sensitization or challenge phase only.

The method also combined measurement of changes in Ca2+i using fl

The method also combined measurement of changes in Ca2+i using fluo-4 and excitation at 490 nm. Results:  After establishing loading conditions, a linear relationship was demonstrated between Em and fluorescence signal in FRET dye-loaded HEK cells held under voltage clamp. Over the voltage range from −70 to +30 mV, slope (of FRET signal vs. voltage, m) = 0.49 ± 0.07, r2 = 0.96 ± 0.025. Similar data were obtained in cerebral artery SMCs, slope (m) = 0.30 ± 0.02, r2 = 0.98 ± 0.02. Change in FRET emission ratio over the holding potential of −70 to +30 mV was 41.7 ± 4.9% for HEK cells and 30.0 ± 2.3%

for arterial SMCs. The FRET signal was also shown to be modulated by KCl-induced depolarization Tyrosine Kinase Inhibitor Library chemical structure in a concentration-dependent manner. Further, in isolated arterial SMCs, KCl-induced depolarization (60 mM) Selleckchem Deforolimus measurements occurred with increased fluo-4 fluorescence emission (62 ± 9%) and contraction (−27 ± 4.2%). Conclusions:  The data support the FRET-based approach for measuring changes in Em in arterial SMCs. Further, image-based measurements of Em can be combined with analysis of temporal changes in Ca2+i and contraction. “
“Please cite this paper as: Zhang (2011). Effect

of Suspending Viscosity on Red Blood Cell Dynamics and Blood Flows in Microvessels. Microcirculation 18(7), 562–573. To obtain a better understanding of the beneficial effect of high plasma viscosity observed in hemodilution and resuscitation experiments, we conducted a computational study to investigate

the suspending viscosity effect on red blood cell (RBC) dynamics and blood flow behaviors in microvessels. For single RBCs in simple shear or channel flows, RBCs appear more flexible as indicated by the tank-treading motion in shear flows and the strong transverse migration in channel flows. For the multiple RBC flows in straight channels, our results indicate no significant change with the suspending viscosity in stable flow structure and hemorheologic behaviors, under both constant Methisazone flow and forcing conditions. However, due to the increase in apparent cell deformability in a more viscous medium, the cell-free layer (CFL) can be established in a shorter distance along the channel. Considering the multilevel bifurcated structure of the microvascular network, this change in CFL development distance may affect the phase skimming and RBC separation processes at the downstream bifurcation, and therefore the microcirculation performance in the tissue. This may suggest a possible mechanism for the high functional capillary density associated with a high suspending viscosity observed in experiments. “
“Please cite this paper as: Folkesson KT, Samuelsson A, Tesselaar E, Dahlström B, Sjöberg F.

3B) Using PCR to isolate the complete cDNA of CLEC12B from PBMC,

3B). Using PCR to isolate the complete cDNA of CLEC12B from PBMC, we found the mRNA of this molecule to be differentially spliced (Fig. 3C). Four different splice variants of CLEC12B were detected resulting from two independent differential splicing events. Splice variant A codes for a protein that shows the canonical lectin-like structure consisting of an intracellular domain, a transmembrane domain and a stalk domain encoded by one exon each followed by three exons coding for three CTLD. A differential

splicing event at the 3′-end of the second CTLD exon leads to an extension of this exon which contains a stop codon giving rise to a protein lacking the last of the three CTLD (variant B). A second differential splicing event does not join BGB324 the transmembrane coding exon to the 5′-end of the stalk exon but instead uses a potential splice site 8 bp further downstream in the stalk exon. This selleckchem causes the deletion of 8 bp of the mRNA resulting in a frame shift and the immediate stop of translation. The putative resulting proteins contain only the cytoplasmatic and transmembrane domains (variant C and D). Because these differential splicing events also give rise to truncated, potentially non-functional proteins, it was of interest not only to determine the overall expression

levels of CLEC12B but also to discriminate especially between putative functional and non-functional isoforms using different sets of primers. As shown in Figure 3D isoforms A and B of CLEC12B are not expressed by HUVEC, the myeloid–erythroid line K-562, the B-cell lines 721.221 and RPMI 8866, and the NK cell line NK-92. Low expression could be detected in DC, the monocytic lines U-937 and Mono-Mac-6 and the T-lymphocyte line Jurkat. The T-lymphocyte line CCRF-CEM expressed the highest levels of mRNA. In general, the majority of the transcripts detected in these cells contain the 8- bp deletion in the stalk exon probably rendering the translated product non-functional. Only CCRF-CEM cells express substantial levels of CLEC12B mRNA that probably code for a functional protein (Fig. 3D). Thus, it seems that CLEC12B RVX-208 and CLEC9A do not display

the myeloid-specific expression observed for CLEC-1, CLEC-2 and DECTIN-1 but are more broadly expressed in the myeloid as well as the lymphocyte lineage. The C-type lectin-like receptors CLEC-1, CLEC-2 and DECTIN-1 are known to be expressed in DC [14, 40, 41], and DECTIN-1 has been shown to be downregulated upon activation of DC [14, 42]. We therefore investigated the regulation of CLEC12B and CLEC9A in comparison with DECTIN-1, CLEC-1 and CLEC-2 in DC after treatment with various maturation stimuli. To this end, DC derived from CD34+ cord blood cells were treated with LPS, Zymosan A, anti-CD40 mAb cross-linked by F(ab’)2-fragments of goat anti-mouse IgG and INF-γ for 6 h, and mRNA levels were measured using real-time RT-PCR.