The opinions expressed herein are those of the authors and should not be construed as the official policy of the NIH. Overlapping

WNV peptide arrays were obtained through the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH. We thank Dr. Thomas Monath (Acambis, click here Inc.), Dr. Alan Barrett (UTMB, Galveston) and Dr. Kristen Bernard (Wadsworth Center, Albany, NY, USA) for kindly providing JEV SA14-14-2, JEV Beijing and WNV 3356, respectively. We thank Dr. Michael Brehm for technical advice and Dr. George Reed and James Potts for assistance with statistical analysis. We also thank Dr. Alan Rothman, Dr. Anuja Mathew and Dr. Mary Co for helpful advice and comments with regard to experimental design and manuscript review. Conflict of interest: The authors have no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available

as submitted by the authors. “
“A diagnosis of idiopathic anaphylaxis following a detailed clinical assessment remains very challenging for patients and clinicians. Risk reduction strategies such as allergen avoidance are not possible. This study investigated find more whether the (ISAC) allergen array with 103 allergens would add diagnostic value in patients with idiopathic anaphylaxis. We extended the specific immunoglobulin (Ig)E testing in 110 patients with a diagnosis of idiopathic anaphylaxis from five UK specialist centres using ISAC arrays. These were divided into three groups: score I identified no new allergen sensitization beyond those known by previous assessment, score II identified new sensitizations which were not thought likely to explain the anaphylaxis and score III identified new sensitizations felt to have a high likelihood of being responsible for the anaphylaxis. A proportion (50%) of score III patients underwent clinical reassessment to substantiate the link to anaphylaxis in this group. The results show that 20% of the arrays were classified as score III with a high likelihood Celecoxib of

identifying the cause of the anaphylaxis. A wide range of major allergens were identified, the most frequent being omega-5-gliadin and shrimp, together accounting for 45% of the previously unrecognized sensitizations. The ISAC array contributed to the diagnosis in 20% of patients with idiopathic anaphylaxis. It may offer additional information where a careful allergy history and follow-on testing have not revealed the cause of the anaphylaxis. “
“Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium–potassium–adenosine–triphosphatase pump (Na+/K+-ATPase). Water follows to maintain iso-osmolar conditions and to keep alveoli dry.

26 The subsequent reinstatement of the IL-4 response at day 7, in conjunction with falling IL-10 production, is fully consistent with the auto-regulatory action of the latter cytokine.26 A sub-group of the donors (33%) reacted to TG with high CD4+ T-cell proliferation and IFN-γ production rates, similar those seen upon TT stimulation. On the other hand, the profile for all other cytokines was indistinguishable from

that of the TG ‘low IFN-γ responders’, indicating that the breakaway from an essentially regulatory response was only partially successful. In selleck chemical an earlier study, however, where the concentration of TG employed was threefold higher than that used here, normal PBMC produced significant quantities of IL-2 (at day 1), IFN-γ and IL-5 (days 5 and 7) as well as approximately twofold lower amounts of IL-10.13 Hence, at higher levels of autoantigenic stimulation, the regulatory effect of the initially produced IL-10 may be overridden. We have previously reported that normal or even slightly elevated IL-10 responses accompany exaggerated TG-induced Th1 responses in patients with Hashimoto’s thyroiditis and Graves’ disease,13 suggesting that a pathological

outcome of T-cell responses to TG may depend on the balance between Th1 cytokines and IL-10, rather than on a lack of IL-10 production. In this connection, it would be of interest CP-673451 molecular weight to establish whether the high production of IFN-γ exhibited

by one-third of the donors, in response to TG, is associated with enhanced risk for the development of autoimmune thyroid disease. On day 1, after challenge with TG, monocytes were identified as the primary producers of IL-10 (see Figs 4 and 5), although a small population of IL-10-secreting CD4+ T cells with memory phenotype was also detected. Notably, depletion of CD3-positive cells, from the PBMC employed, abrogated find more the IL-10 response, indicating that TG-specific T cells exert a decisive influence in steering the monocyte response towards this antigen in an anti-inflammatory direction. The fact that cytokine production in response to TG differs so markedly in degree from that seen with KLH (as a primary antigen of comparable size), and in character from that observed with TT, strongly suggests that experienced T cells of a regulatory phenotype may be orchestrating the response. The development of such IL-10 memory responses has been shown to arise from repetitive stimulation of T cells via the T-cell receptor, resulting in their repeated exposure to IL-4.27,28 As an indigenous (auto-)antigen, TG should be ideally suited to provide such stimulation. In summary, TG induces in vitro a rapid proliferative response by peripheral CD4+ T cells from normal healthy individuals, indicative of previous in vivo experience of the antigen.

Although IL-17+ γδ T cells develop exclusively before birth, they persist in adult mice as long-lived

cells with self-renewing capacity [10]. Marie-Laure Michel from Adrian Hayday’s group (London, UK) presented data supporting a novel role for IL-7/IL-7R signalling, via phosphorylation of STAT3, in the selective development and buy AZD1208 expansion of the IL-17+ γδ T-cell subset in mice and in humans (where this subset has proved highly elusive). Her colleague Mélanie Wencker showed that SKG mice, hypomorphic for the ZAP-70 signal transducer, have significantly reduced IL-17+ γδ T-cell compartments in the thymus and in the periphery, thus suggesting a previously underestimated requirement for TCR signalling for these cells’ development. However, Nital Sumaria from Dan Pennington’s lab (London, UK) demonstrated that in foetal thymic organ cultures neither TCR cross-linking with an activating antibody nor ligand-independent signalling from a γδ TCR lacking variable domains favours the generation of CD27− IL-17+ γδ cells (but rather their CD27+ IFN-γ+ counterparts). Thus, the mechanism

underpinning the development of IL-17+ γδ T cells appears complex and warrants further investigation. In contrast, the development of DETCs (which make IFN-γ but selleck screening library not IL-17) clearly requires TCR agonist selection in the murine thymus [11]. Gleb Turchinovich (Hayday group) provided evidence that agonist encounter, instead of deleting developing γδ thymocytes, sets a very high threshold for DETC activation, which may therefore only occur in conditions of very abundant cytokine or costimulatory receptor expression. Craig Morita (Iowa City, IL, USA) presented comprehensive microarray analyses of human Vγ9/Vδ2 T-cell subsets, demonstrating that early central/memory cells are characterised by the expression of CXCR6, CCR1 and CCR2 whereas late effector/memory cells express CXCR1, CXCR2 and CX3CR1. These data suggest Phosphoglycerate kinase fundamental differences in the recruitment of functionally distinct Vγ9/Vδ2 T-cell populations to sites of inflammation. Karin Schilbach (Tübingen, Germany) proposed that

a CD4+ CD34+ subset of human Vδ1+ T cells may “trans-differentiate” into αβ T cells when submitted to a particular activation regimen in vitro. This is accompanied by RAG1/2, TdT and pTα re-expression and TCRα rearrangement, thus leading to the generation of CD4+ or CD8+ αβ T cells. Schilbach provocatively suggested that this could constitute a rapid source of αβ T cells at sites of inflammation when normal thymic differentiation or peripheral homeostasis would be impaired. To foster interactions between researchers working on γδ or αβ T cells, the organisers invited the EU FP7 consortium SYBILLA (systems biology on T-cell activation) to participate in this meeting. SYBILLA uses systems biology approaches to understand the early steps of αβ T-cell activation and differentiation [12].

albicans colonies may suggest correlation between candidal colony counts in the vagina of mother and Candida colonisation in the neonate.

Perinatal risk factors for neonatal colonisation were maternal colonisation and vaginal delivery. It has been reported that low gestational age (<32 week) and very low birthweight (<1500 g) are risk factors for neonatal Candida colonisation.[5, 18, 20] We did not confirm these findings, but in our cohort there was only one neonate with very low birthweight (1420 g) and two neonates with low gestational age (lower gestational age 32 weeks). Our study demonstrated that early Candida colonisation of the neonate seems to occur through vertical transmission PCI 32765 in the first 72 h of life. However, we did not investigate horizontal transmission from other sources. Furthermore, we did not swab all infants later on (especially on 7th day) to explore the full process of colonisation. Nevertheless, our findings strongly suggest that early neonatal colonisation by C. albicans occurs through vertical transmission, during or immediately after birth, and that horizontal transmission is not the principal mode of colonisation in the very first days of life. None for Anthoula Filippidi, Emmanouil Galanakis, CHIR-99021 ic50 Sofia Maraki, Irene Galani, Maria Drogari-Apiranthitou, Maria Kalmanti, Elpis

Mantadakis. Dr G. Samonis has received fees for speaking, for organising education, reimbursement for attending symposiums, funds for research, fees for serving IMP dehydrogenase on an advisory board from companies Pfizer, Gilead, Astellas and MSD. “
“The cut-off values of immunological tests employed in diagnosis

of allergic bronchopulmonary aspergillosis (ABPA) have never been validated. Herein, we compare the immunological findings in patients with ABPA and asthma using receiver operating characteristic analysis. Consecutive asthmatic subjects underwent all the following investigations: Aspergillus skin test, IgE levels (total and A. fumigatus-specific), Aspergillus precipitins, eosinophil count, chest radiograph and CT chest. There were 372 subjects (179 men, mean age 35.9 years) with a mean asthma duration of 8 years. ABPA was diagnosed in 76 patients (64 bronchiectasis, 12 without bronchiectasis). ABPA was separated from asthma using the best cut-off values of total IgE, A. fumigatus IgE and total eosinophil count of 2347 IU ml−1, 1.91 kUA l−1 and 507 cells per μl respectively. The sensitivity/specificity of these parameters were 87/81%; 99/87%; and, 79/76% respectively. The corresponding AUC values were 0.95, 0.90 and 0.82 respectively. The combination of these three tests at the aforementioned cut-offs provided 100% specificity. Our study provides evidence-based cut-off values of IgE (total and A. fumigatus-specific) and eosinophil counts in differentiating ABPA from asthma.

15,16 Recently, it has been shown that the recovery of GFR within 1 month of delivery is largely attributable to recovery of filtration capacity. Moran et al. were able to show that all elements of GFR control, that is, blood flow, surface area and transfer coefficients, are altered in preeclampsia17 and that changes in basement membrane size-selectively

are relevant to the development of proteinuria. The estimation and subsequent quantification of proteinuria https://www.selleckchem.com/products/crenolanib-cp-868596.html remains a challenge in preeclampsia diagnosis. Much work has been done to validate a spot urine test of protein : creatinine ratio to establish a firm diagnosis of proteinuria18 compared with the clinical ‘gold standard’ of a 24 h urine collection for protein assessment. The threshold for abnormal protein excretion is increased to 300 mg per day, or 30 mg/mmol creatinine.19 This threshold is an all or none categorization of renal involvement as there has been no evidence that the foetal or maternal outcomes are directly related to the degree of proteinuria. In everyday clinical practice the spot test has the ease of collection but requires local validation; in some centres the protein creatinine ratio is still questioned in terms of reliability.20 In contrast to spot urinary protein : creatinine

ratios performed outside of pregnancy, during pregnancy there is a loss of the diurnal variation of protein excretion.21 The use of the 24 h test is fraught with INCB024360 difficulties resulting in inaccuracies.22

In pregnancy the physiological dilatation of the ureters and incomplete bladder emptying as a result of the enlarging uterus can cause significant collection errors.18 These errors can be avoided by ensuring adequate hydration and standardization of the collection technique (discarding urine at the beginning of the collection and lying in left lateral recumbency for 45 min at the end of the collection to remove any partial obstruction related to supine or upright posture).18 The renin-angiotensin-aldosterone system (RAAS) has been investigated in preeclampsia. The normal physiological response of the RAAS in pregnancy is an increase in circulating renin, angiotensinogen, angiotensin II and aldosterone.7,23 Pregnant women are check details resistant to the pressor effects of angiotensin and despite these changes remain normotensive throughout pregnancy. In contrast, women with preeclampsia have normal or below normal levels of renin, aldosterone and angiotensin II.23–25 Despite these hormonal changes in women with preeclampsia, they paradoxically have a reduction in plasma volume.26 The decline in plasma volume occurs several weeks prior to the rise in blood pressure and the other clinical manifestations of preeclampsia. Despite the decline in plasma volume prior to the onset of disease, women who will develop preeclampsia do not salt waste but do demonstrate an exaggerated diuresis in response to sodium loading.

05 is considered significant. We thank T. Kaiser and J. Kirsch for FACS sorting; and R. S. Jack for discussion of the data and J. J. Lee (Mayo Clinic, Scottsdale, USA) for anti-mouse MBP antibody. This work is supported by the Deutsche Forschungsgemeinschaft (BE 1171/2-1). Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“CD8+ T cells play an important role in controlling pathogenic infections and are therefore key players in the immune response. It has been shown that among other factors CD4+ T cells can shape the magnitude as well as the

quality of primary and/or secondary CD8+ T-cell responses. However, due to the complexity and the differences among diverse immunization or infection models, the overall requirement, the time points, as well as the specific mechanism(s) of CD4+ T-cell help may differ substantially. Here, we summarize current knowledge about Tyrosine Kinase Inhibitor Library selleckchem the differential requirement of CD4+ T-cell help in promoting primary CD8+ T-cell responses as well as establishing functional memory CD8+ T cells in various experimental settings. A number of different parameters influence, by virtue of their strength and composition, CD8+ T-cell activation; they subsequently also shape the size and the phenotypical and functional properties of the resultant memory CD8+ T-cell pool. These parameters

include antigen-specific T-cell precursor frequencies [[1]], the strength of the T-cell receptor interaction with peptide–MHC complexes, and the signals provided by co-stimulatory receptors, as well as innate immune system derived inflammatory cytokines

[[2, 3]]. Among the factors that modulate the activation of dendritic cells (DCs), the cells that are the main inducers of CD8+ T-cell responses, is the help provided by CD4+ T cells. CD4+ T-cell engagement of DCs promotes the upregulation of certain co-stimulatory molecules (such Methane monooxygenase as CD80 and CD86) on, as well as the release of pro-inflammatory cytokines such as IL-12 by, DCs. Thus, in many defined experimental settings, T helper cells have been implicated in the expansion and survival of CD8+ T cells during the primary response, and have a key role in establishing long-lived, functionally robust memory CD8+ T-cell responses [[4-7]]. The concept of T-cell help for CD8+ T-cell responses was further supported by the finding that chemokines secreted by activated CD4+ T helper cells can play a key role in the recruitment of naïve antigen-specific CD8+ T cells to antigen-bearing antigen presenting cells (APCs) in secondary lymphoid organs [[8]] or to sites of infection [[9]]. Moreover, in some experimental settings CD4+ T cells were proposed to directly interact with CD8+ T cells, thereby promoting their activation and expansion [[10]].

From superoxide, other ROS, such as hydrogen peroxide, can be generated. The exact mechanism of pathogen killing within the phagosome is not known. From the killing defect seen in CGD phagocytes, it is clear that ROS play an important role, but whether this is a direct role through formation of hypochlorous acid from hydrogen

peroxide and chloride, catalysed by myeloperoxidase, or an indirect role through facilitating the release of proteolytic enzymes from the granules in the phagocytes [2], or a combination of these mechanisms, remains to be established. Most CGD pathogens share the property Palbociclib of producing catalase; as such, they degrade the hydrogen peroxide that they themselves generate. It has therefore click here been suggested that catalase-negative organisms, by supplying the CGD phagocytes with microbial hydrogen peroxide, might complement the hydrogen peroxide deficit in CGD phagocytes, thus inducing killing of the microbes themselves. Catalase production was thus thought

to be an important microbial pathogenicity factor in CGD. However, this hypothesis must be viewed in the context that the majority of all pathogens contain catalase (with the important exception of streptococci). This view has been challenged further by the retained virulence of Aspergillus and staphylococci rendered genetically deficient for catalase production [3, 4]. In addition, individuals with the quite common deficiency of myeloperoxidase do not suffer from CGD-like symptoms. The genes encoding the five NADPH oxidase components are CYBB (located on the X chromosome)

for gp91phox, and the autosomal genes CYBA for p22phox, NCF1 for p47phox, NCF2 for p67phox and NCF4 for p40phox (Table 1). About 70% of the CGD patients have a mutation in CYBB (most of them hemizygous males, Farnesyltransferase but a few heterozygous females with skewed expression of their mutation are also known). The remainder of the patients have a mutation in NCF1 (about 20%), in CYBA (about 5%) or in NCF2 (about 5%). Only one patient is known with a mutation in NCF4. A mutation in any of these five genes can cause CGD. If the mutation leaves some residual NADPH oxidase activity intact, the clinical expression of the disease is less serious [5] and the chance of survival of the patient is larger [6] than in the case of total oxidase deficiency. This depends upon the gene mutated, the type of mutation and the position of the mutation within the gene. In general, mutations in NCF1 lead to a milder form of CGD (later presentation, milder clinical expression, better chance of survival) than mutations in any of the other genes. For genetic counselling and prenatal diagnosis, mutation analysis of the CGD genes is mandatory. Treatment should be started immediately after CGD has been definitely diagnosed, or even before.

Furthermore, we could show that pharmacological inhibition of SphK results in reversal of CXCL4-induced monocyte survival, cytokine expression, and release of oxygen radicals, which was confirmed by the use of SphK1-specific siRNA. CXCL4-mediated rescue from apoptosis, which is accompanied by inhibition of caspases, is controlled by SphK1 and its downstream

element Erk. Taken check details together, these data assign SphK1 as a central regulator of acute and delayed monocyte activation and suggest SphK1 as a potential therapeutic target to suppress pro-inflammatory responses induced by CXCL4. Monocytes are members of the mononuclear phagocyte system and represent one of the most flexible cell types within the immune system. These cells are critically important in the regulation of innate and adaptive immune responses by generation of inflammatory mediators, antigen presentation, phagocytosis, and killing of microorganisms. Monocytes are highly mobile cells and can rapidly accumulate at sites of inflammation. However, a successful defense requires not only the presence of monocytes at inflammatory sites but also fast and

effective mechanisms for their activation. In previous reports we described monocyte activation by CXC chemokine ligand 4 (CXCL4; platelet factor 4) 1–3. CXCL4 belongs to the family of CXC-chemokines and is rapidly released find protocol in high concentrations upon platelet activation 4, 5. Although no data exist

in the literature concerning CXCL4 concentrations at a site of acute platelet activation in vivo, normal serum concentrations of CXCL4 (1–2.5 μM) 6 are sufficient to induce a full monocyte response 1. Moreover, in regions of acute platelet activation where such platelet–monocyte interaction may take place, concentrations of CXCL4 are likely to be much higher. Although CXCL4 does not induce typical chemokine responses such as chemotaxis or calcium mobilization in monocytes, CXCL4 induces ROS formation, increases phagocytosis, and protects these cells from undergoing spontaneous apoptosis Flavopiridol (Alvocidib) 1, 2. Furthermore, CXCL4 treatment provokes monocytes to express and to release several pro-inflammatory cytokines and chemokines 1, 3, and stimulates the differentiation of these cells into a specific subtype of macrophages lacking HLA-DR on their surface 1. In contrast to typical CXC-chemokines, which transduces their signals via binding to a 7-transmembrane-domain G protein-coupled receptors, CXCL4-induced monocyte activation is mediated by binding to a chondroitin sulfate proteoglycan expressed on the latter cells 2, neutrophils 7, 8, T cells and mast cells (our unpublished results). It should be mentioned here that CXCR3-B, which has been described as functional CXCL4 receptor on endothelial cells 9 is not expressed on monocytes or neutrophils 2.

3D). Finally, to confirm that LTi-like cell survival in vitro did not require IL-7, LTi prepared

from Rag−/−γc−/− mice (therefore unresponsive to IL-7) were cultured with CD45−podoplanin+ SSCL and in this assay survival was not affected (Fig. 3C). To examine whether adult LTi-like cells were able to survive without IL-7 or γc cytokine survival factors within AZD1208 clinical trial the splenic T zone in vivo, tissue sections of spleen from IL-7−/− and Rag−/−γc−/− mice were stained for LTi-like cells and analyzed by immunofluorescent confocal microscopy. In both types of mice, LTi-like cells were distributed within the splenic T zones and these cells were in close proximity with VCAM-1+ stroma of T-cell areas suggesting interactions between LTi-like cells and surrounding T-zone stroma (Fig. 3E). Together, these data provide evidence that splenic adult LTi-like cells are able to survive in vivo in an IL-7-independent manner. In the embryo, IL-7 is important in controlling numbers of LTi. In transgenic Ipatasertib mice expressing high levels of IL-7, LTi numbers are greatly increased, resulting in increased numbers of Peyer’s patches and ectopic LN 20. Current data indicate that IL-7 improves embryonic LTi survival. Our previous studies have demonstrated that LTi persist in the adult spleen of IL-7−/− and γc−/− mice 18. In this study we identified IL-7Rα+ and IL-7Rα−

LTi-like cells in adult spleen. We found that CD45−podoplanin+ SSCL promote the survival of adult LTi-like cells in an IL-7 independent manner, and that LTi-like cells isolated from Rag−/−γc−/− Phosphoglycerate kinase mice survived well in culture with CD45−podoplanin+ SSCL. Finally, splenic LTi-like cells exist in IL-7−/− and γc−/− mice in situ and these cells remain in the white pulp areas where they interact with VCAM-1+ T-zone stroma which express podoplanin. Taken together these data suggest that stromal-derived factors control the survival

of LTi in the adult. While IL-7 plays a key role in vivo, there appears to be redundancy in the signals supporting LTi-like cell survival in the adult spleen. All experiments were performed in accordance with UK laws and with the approval of the University of Birmingham ethics committee. C57Bl6, RAG2−/−, RAG2−/−/commonγchain−/− (Rag−/−γc−/−) and CD3ε-transgenic (CD3εtg) mice were all bred and maintained in the Biomedical Services Unit at the University of Birmingham. CD3εtg mice have a profound block in the early T-cell development at the CD4−CD8−CD25−CD44+ stage in the thymus and display a complete loss of T-lymphocytes 21. Mouse spleens were excised and digested in RPMI 1640 medium with 10% FCS plus 1 mg/mL collagenase/dispase (Roche) and 20 μg/mL DNase 1 (Sigma) at 37°C for 20 min. To aid digestion, tissues were agitated to disperse aggregates.

Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper Rapamycin molecular weight is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells. The objective of this study was to investigate the kissper influence on intestinal inflammation using cultured cells and ex-vivo tissues from

healthy subjects and Crohn’s disease (CD) patients. The anti-oxidant and anti-inflammatory properties of kissper were tested on Caco-2 cells and on the colonic mucosa from 23 patients with CD, by challenging with the lipopolysaccharide from Escherichia coli (EC-LPS) and monitoring the appropriate markers by Western

blot and immunofluorescence. EC-LPS challenge determined an increase in the intracellular concentration of calcium and reactive oxygen species (ROS). The peptide kissper was highly effective in preventing the increase of LPS-induced ROS levels in both the Caco-2 cells and CD colonic mucosa. Moreover, it controls the calcium increase, p65-nuclear factor (NF)-kB induction and transglutaminase 2 (TG2) activation inflammatory response in Caco-2 cells and CD colonic mucosa. Kissper efficiently counteracts the oxidative ABT-199 mw stress and inflammatory response in valuable model systems consisting of intestinal cells and CD colonic mucosa. This study reports the first evidence supporting a possible

correlation between some beneficial effects of kiwi fruit and a specific protein molecule rather than generic nutrients. “
“Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation. Dendritic cells are important as key regulators of innate and adaptive immune responses. Using a new whole blood assay we investigated functional Decitabine clinical trial characteristics of blood plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC) and monocytes in rhesus macaques by studying induction of activation markers and cytokine expression upon Toll-like receptor (TLR) stimulation. In a head-to-head comparison we observed that rhesus macaque venous blood contained relatively lower numbers of pDC than human venous blood, while mDC and monocytes were present at similar percentages. In contrast to humans, pDC in rhesus macaques expressed the interleukin (IL)-12p40 subunit in response to TLR-7/8 as well as TLR-9 stimulation. Expression of IL-12p40 was confirmed by using different monoclonal antibodies and by reverse transcription–polymerase chain reaction (RT–PCR).