As well as these new developments, there also appears to be a protective role for women taking progestogen-only birth control pills, particularly those with anti-gonadotrophic activity such as norethisterone [25]. In summary, it is hoped that this and future audits will serve to help inform the decision-making process in planning future care for patients with bradykinin-mediated angioedema. The British Society for Immunology Clinical Immunology and Allergy Section (BSI-CIAS) received an unrestricted grant buy MLN0128 of £5000 from Shire to support data entry. S. J. is supported by an NISCHR Fellowship. S Jolles – Consulting, speaker, meeting support from Shire, CSL Behring, Viropharma and SOBI. P Williams – No disclosure

E Carne – Meeting support CSL Behring and Shire. H Mian – No Disclosure A Huissoon – Meeting support CSL Behring, Shire and Viropharma. Consulting Viropharma. G Wong – No Disclosure S Hackett – Meeting support CSL Behring J Lortan – No disclosure V Platts – No Disclosure H Longhurst and S Grigoriadou and members of their department have received funding to attend conferences and other educational events, have acted as medical advisor or speaker, have received donations to her departmental fund, have received financial and other assistance with patient care projects and/or have participated in clinical trials with the following companies: CSL Behring, Pharming/Swedish

Orphan, Jerini/Shire, IWR-1 datasheet Dyax, Viropharma, Baxter and Grifols. J Dempster – Performed consultancy work for Virophrama,

Vasopressin Receptor Shire and CSL Behring S Deacock – No disclosure S Kahn – No Disclosure J Darroch – Meeting support Shire C Simon – No Disclosure M Thomas–No Disclosure V Pavaladurai – No disclosure H Alachkar – No Disclosure A Herwadkar – No Disclosure M Abinun – No Disclosure P Arkwright – No Disclosure M Tarzi – Speaker and travel support CSL Behring and Shire. M Helbert – Speaker, consulting, conference support CSL Behring, consulting and conference support Shire and consulting Viropharma. C Bangs – No Disclosure C Pastacaldi – No Disclosure C Phillips – Consulting for Viropharma H Bennett – Consulting for Viropharma T El-Shanawany – Consulting and meeting support from Shire, CSL Behring and Viropharma. “
“The present authors have previously reported that Vibrio mimicus expresses 77-kDa and 80-kDa outer membrane proteins in response to iron-limited conditions, and that the 77-kDa protein serves as the receptor for ferriaerobactin. In this study, it was found that V. mimicus can use heme and hemoglobin as iron sources. FURTA was then applied to V. mimicus 7PT to obtain candidate gene fragments involved in utilization of heme and hemoglobin. One FURTA-positive clone was shown to contain a partial gene, whose predicted amino acid sequence correlated with the N-terminal amino acid sequence determined for the 80-kDa outer membrane protein and also shared homology with heme/hemoglobin receptors of Gram-negative bacteria.

Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver–operator curve (ROC) analysis and area under curve (AUC). Reproducibility

was assessed by coefficient of variation (CV). Results:  Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% selleck chemicals llc of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). Conclusion:  LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available. “
“Fetuin-A (Fet-A) is an important regulator

of extracellular matrix mineralization. Fet-A plays a critical role in the formation and stabilization of high molecular weight colloidal protein–mineral complexes known as calciprotein particles (CPP). The aim of this study was to examine the effects of inflammation, renal function and dialysis modality on serum Fet-A and CPP. This is an observational study of patients with chronic kidney disease (CKD) and those with chronic inflammatory Raf inhibitor disease (CID) but normal renal function. Serum CPP were quantified indirectly by analysing the apparent reduction in serum Fet-A concentration (reduction ratio, RR) after high-speed centrifugation. Serum total Fet-A concentrations are reduced in renal disease and in patients with CID. CPP were not detectable in the serum of normal individuals. CPP represent an increasing percentage of total circulating Fet-A concentrations in patients with CID (RR, 13.3 ± 8.5%), as well as in patients with pre-dialysis CKD (12.4 ± 7.3%) and those

undergoing peritoneal dialysis (RR, 22.8 ± 6.0%) or haemodialysis (RR, 38.1 ± 12.8%). The highest Fet-A RR were found in patients with calcific uraemic arteriolopathy (CUA) on haemodialysis (73.9 ± 15.6%). Serum total Fet-A Thiamet G concentrations and Fet-A reduction ratios decreased during a single haemodialysis session, by 24% (P < 0.001) and 34% (P < 0.001), respectively. Inflammation appears to be associated with mineral stress even in the absence of renal dysfunction. Patients with CUA on haemodialysis have very high serum Fet-A reduction ratios, suggesting that this measurement may have a prognostic/diagnostic role in this condition. Vascular calcification (VC) has long been observed in normal ageing and in disease.[1] However, over the last decade it has emerged as an important mediator of cardiovascular dysfunction and predictor of adverse outcomes in various patient groups.

The recipient vessels were digital artery and dorsal digital vein. The flap was not reinnervated during transfer procedures. The donor sites were closed primarily in all cases. Flap size ranged from 15 × 25 mm to 60 × 20 mm. All flaps BYL719 concentration were survival. Partial loss occurred in one flap, due to venous congestion caused by excessive stitch tension. The donor sites healed unevenfully

in eight cases, but mild wound dehiscence occurred in two cases. The follow-ups ranged from 6 to 29 months with the mean of 18.1 months. The mean of s-2PD and m-2PD were 8.8 mm and 6.8 mm at patients’ last visits, respectively. MPAP flaps are good in terms of general morbidity, cosmetic results, and durability. This flap is a valuable alternative method

of repairing the glabrous finger pulp and tip defects. © 2009 Wiley-Liss, Inc. Microsurgery, 2010. “
“Preoperative CT-angiography (CTA) has shown to reduce operative time in deep inferior epigastric perforator (DIEP) flap breast reconstruction compared to Doppler ultrasonography (US). Although decreased flap loss has been suggested, statistical significant reduction remains indeterminate. The purpose of this review is to evaluate flap loss after preoperative CTA and Doppler US in DIEP-flap breast reconstruction. A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane libraries. All articles comparing CTA to Doppler US were selected and critically appraised; Alectinib manufacturer data on flap loss were extracted. From 678 studies, eight were selected for appraisal. Six case–control studies were included in the final analysis. Pooled

analysis showed CTA resulted in a significant reduction Selleck Decitabine in partial necrosis (odds ratio/OR 0.15; 95% confidence interval/CI 0.07–0.32, P < 0.0001) and decreased flap loss (OR 0.28; 95% CI 0.10–0.79, P = 0.02). Studies included in this meta-analysis have several limitations. However, most studies find a large clinical advantage of CTA over Doppler US, which reaches statistical significance when combined. As results show that CTA prior to DIEP flap breast reconstruction offers significant clinical benefits, we suggest the routine use of preoperative CTA. © 2013 Wiley Periodicals, Inc. Microsurgery 33:496–502, 2013. "
“Microvascular free tissue transfer is a reliable technique for head and neck reconstruction with success rates of 90–99%. Currently, there is no consensus concerning antithrombotic agents, antibiotics, or monitoring techniques. Therefore, the aim of this study was to review current literature dealing with microvascular free-tissue transfer and factors influencing the outcome. In addition to excellent microsurgical techniques, coupling devices are a promising new technique, but are not useful in all arteries. Antibiotics should be given in three doses, as a more lengthy dosage time seems to have no advantage.

These patterns were observed regardless of treatment protocol (anti-GITR mAb and anti-CD25 mAb), strain (BALB/c check details and C57BL/6) and antigen (SRBC, IAV and PE). Importantly, these findings provide a basis to explain the marked increase in serum antibodies, especially switched isotypes, upon in vivo Treg-cell disruption or depletion. These data are also consistent with reports showing the ability of adoptively transferred Treg cells to suppress in vivo B-cell responses,21,30–42 including GC reactions32,41 and the generation of antibody-forming cells.33,34,36

Although it is clear that Treg cells participate in the control of GC reactions, the target and site of Treg-cell action are currently unknown. Two likely targets are Tfh cells and GC B cells. The Tfh cells are critical in the induction and maintenance of GCs because they provide key co-stimulatory signals through inducible T-cell costimulator (ICOS) and CD154, as well as key cytokines, especially IL-21.75 In

addition, it has been shown that the magnitude of the GC response is directly linked to the size of the induced Tfh-cell pool.76 While Treg-cell suppression of CD4+ T-cell activity is well established,11–13 few investigators have focused on whether Treg cells can specifically alter Tfh function. In a recent study by Erikson and co-workers, however, adoptive transfer of antigen-specific Treg cells was found to down-modulate Cisplatin manufacturer the expression of ICOS on Tfh cells.41 In addition, Weiner and colleagues reported that induction of Treg cells in vivo compromised the ability of Tfh cells to produce optimal levels of IL-21.39 As ICOS expression77 and IL-21 production78–80 by Tfh cells are crucial for optimal B-cell differentiation and switching, influencing these molecules would serve as an effective means by which Treg cells could

control the GC response. In preliminary experiments, PIK3C2G we tested whether total numbers of splenic Tfh cells were altered by anti-GITR treatment in SRBC-immunized mice. However, when examining days 8 and 12 (the peak of splenic Tfh-cell induction after antigen challenge), no differences were observed (see Supplementary material, Fig. S4). Germinal centre B cells are also a potential target because a number of studies have demonstrated that Treg cells directly suppress activated B cells in vitro.32,40,42–46 In these experiments, Treg–B-cell contact was required and in several reports, Treg cells effected suppression by killing B cells in either a Fas-dependent43 or granzyme B-dependent40,46 manner. Although Treg cells may indeed directly suppress GC B cells, it is uncertain whether they use a cytotoxic mechanism in vivo. Studies in our laboratory found that both Fas-mutated lpr mice and granzyme B-deficient mice generated normal GC responses after SRBC challenge (data not shown).

1 AR is due to host immune responses towards antigens on the transplanted kidney that are foreign to the host, most importantly the human leucocyte antigens (HLA).2 Incompatible HLA can be recognized by alloreactive T cells through antigen-presenting cells (APC) either of donor organ origin (direct allorecognition) or in recipient host (indirect allorecognition).2,3 Effector host CD4+ and CD8+ T cells then home to the graft where they produce inflammatory cytokines and mediate direct destruction

of graft tissue.4 A number of products of cellular infiltration of the kidney have been studied as potential urinary biomarkers of rejection, including urinary Granzyme B and CD103.5 Other cell types in the kidney are also involved in the rejection process Autophagy inhibitor price and may be useful potential markers for rejection. In particular, tubular epithelial cells (TEC) are able to GPCR & G Protein inhibitor respond to inflammation and provide a rich source of potentially useful biomarkers into the urine for monitoring kidney function following transplant. A biomarker is defined as ‘a cellular, biochemical, molecule or genetic alteration by which a biological process can be recognized and/or monitor and has diagnostic and prognostic

utility’.6 Biomarkers may be membrane molecules (or fragments) shed following cleavage by proteolytic enzymes (either expressed by TEC or by infiltrating leucocytes at the local injury site) or secreted molecules such as cytokines. Such biomarkers may either be constitutively expressed or released by enhanced proteolytic activity present during inflammation, or alternatively, biomarkers may be absent in steady state, but

selectively upregulated during inflammation.7 In addition, oxidative stress, bacterial infection or inflammation, may induce alternate protein synthesis pathways, or induce alternate mRNA splicing, resulting in the secretion of ‘cell-associated’ molecules and peptides into biological fluids.7 Proteins associated with exosomes (100 nm lipid-bound particles) have also been discovered in urine8 and may provide an additional source Enzalutamide cost of biomarkers.9,10 Detection of protein biomarkers generally involves a colorimetric or fluorescent system such as ELISA, Luminex® Beads and flow cytometry. Recently, proteomics have provided a comprehensive protein profile for analysing graft status. The proteomic approach used electrophoresis or chromatography techniques and mass spectrometry of graft biopsies, plasma and urine. Sigdel et al., in a comparative analysis of AR patients’ urine proteomic profiles with those of healthy controls and stable graft function established by Adachi et al.11 and Gonzalez et al.

Moreover, Ly6C+ monocytes are involved in atherosclerosis and can also differentiate into macrophages or myeloid suppressor cells [2]. The role of Ly6C− monocytes remains more elusive. Ly6C− monocytes express high levels of CX3CR1, which allows them to patrol healthy tissues through long-range crawling on the surface of blood endothelium at the luminal side [10], in response to membrane-anchored endothelial CX3CL1 [11]. This interaction is also required

for their survival [11]. They express low levels of CCR2 and migrate less efficiently to inflamed tissues than inflammatory monocytes [12]. They have been ABT-737 nmr proposed to be precursors of resident macrophage populations [13]. Moreover, their human equivalent, the CD16+CD14dim monocytes respond to virus infection through TLR7 and TLR8 (where TLR is

Toll-like receptor) and produce TNF-α, IL-1β, and CC chemokine selleck inhibitor Ligand 3 (CCL3) [4]. A recent article also reported that Ly6C− monocytes were uniquely equipped with high levels of Fcγ receptors involved in antibody-dependent cell cytotoxicity such as FcγR1 and FcγR4 [14]. Finally, they could also have a role in tissue repair and angiogenesis [13]. Monocytes are produced in the BM from macrophage-DC precursor [13]. Upon development, monocytes reach the blood circulation via BM sinusoids. Egress of Ly6C+ monocytes from BM has been shown to be dependent on CCR2. This egress is weak under steady-state conditions but increases massively upon inflammation induced by bacterial infection

[6]. During infections, low concentrations of TLR ligands in the bloodstream drive CCR2-dependent emigration of monocytes from the BM. BM mesenchymal stem cells and CXC chemokine ligand 12 abundant reticular cells rapidly express CCL2 in response to TLR ligands or bacterial infection and induce monocyte egress into the blood [15]. How Ly6C− monocytes reach the peripheral blood is however still unknown. Here, we report that Ly6C− monocytes expressed high levels of sphingosine-1 phosphate receptor 5 (S1PR5), previously involved in BM egress of natural killer (NK) cells [16]. S1pr5−/− mice lack peripheral Ly6C− monocytes. Our data support a role for S1PR5 together with CCR2 in their egress from the BM. Modulation of extracellular S1P levels did not affect monocyte trafficking to the blood while it SPTLC1 reduced T-cell egress from lymphoid organs, showing that S1P receptors regulate the trafficking of monocytes and lymphocytes using different mechanisms. We measured using quantitative RT-PCR the expression of all S1PR in different lymphocyte and monocyte populations sorted by flow cytometry from the BM. S1PR5 showed the highest expression in monocyte subsets. S1PR5 was expressed 30 times higher in Ly6C− monocytes than in Ly6C+ monocytes (Fig. 1). A similar difference in S1PR5 expression between monocyte subsets has been measured using microarrays by the Immgen consortium (http://www.immgen.org/databrowser/index.html) [17].

(L.) amazonensis infection at 4th (528·49 cell/mm2) and 8th weeks PI (586·82 cell/mm2), and the control group (402·99 Talazoparib cell/mm2) (Figure 3). At 4th weeks PI, the Th2 cytokines production under specific antigenic stimulation showed that IL-4 levels in the L. (L.) amazonensis infection (139·61 pg/mL) were higher (P < 0·05) than those in the L. (V.) braziliensis infection (15·68 pg/mL), as well as at 8th

weeks PI when IL-4 was detected in the L. (L.) amazonensis group (14·45 pg/mL) and absence in mice infected with L. (V.) braziliensis (Figure 4a). In a similar way, the IL-10 levels were also higher (P < 0·05) in the L. (L.) amazonensis infection than in the L. (V.) braziliensis infection either at 4th (374·64 and 17·62 pg/mL) or at 8th (26·03 pg/mL and not detected) weeks PI (P < 0·05), respectively (Figure 4b). Concerning the production of Th1 cytokines, the IFN-γ levels were higher (P < 0·05) in the L. (V.) braziliensis infection than in the L. (L.) amazonensis infection either at 4th (174·41 pg/mL and 50·83 pg/mL) or at 8th (454·13 pg/mL and 30·16 pg/mL) weeks PI, respectively (Figure 4c). Production of the Th1/Th2 cytokines under nonspecific antigen stimuli (Concanavalin

A) showed similar profiles in both groups (Figure 4a–c). Concerning the control group, a HKI-272 cell line nondetectable amount of cytokines was observed in the supernatant of lymph node cell cultures under either specific antigen or nonspecific

stimuli, according to the standard curve. The interaction process between Leishmania Amylase parasites and DCs is complex and involves paradoxical functions, which can inhibit or stimulate T-cell response, leading to either progression or control of infection (18). It is assumed that not only the degree of DCs maturation but also specific subtypes and the compartmentalization of the antigen presentation are of critical interest to the quality of T-cell response (19). In the early phase of the Leishmania infection, besides macrophage, three types of DCs, in particular dDC, LC and inflammatory dendritic cells (iDC), can perform the function of antigen-presenting cells; however, it was demonstrated in murine cutaneous leishmaniasis that both dDC and iDC, but not resident LC in the epidermis, are responsible for the transportation of Leishmania antigens to the draining lymph nodes and stimulate the efficient Th1 immune response (9). Together with the above comments, it was demonstrated in the present work that Leishmania species can also be a crucial factor in priming DCs (dDC and LC) function for preferentially modulating an efficient Th1 or a defective Th2 immune responses. First, at 4th weeks PI, an increase in the cellular densities of both DCs populations in the skin of BALB/c mice infected with L. (L.) amazonensis (P < 0·05) in relation to those infected with L. (V.

” Since the inflammation was triggered by an endogenous protein, albeit an abnormal protein due to malfolding, the term “auto-inflammation” was coined. Initially the disease was treated by Ribociclib solubility dmso administration of the soluble TNF-receptor etanercept since, due to the mutation, circulating levels of the soluble receptor are low; however,

subsequently the inflammation has been shown to respond to anakinra 11, 12. Thus, TRAPS emerges as an IL-1-mediated disease. In some studies, neutralization of TNF-α with infliximab has worsened the inflammation of TRAPS 13. The second disease that was considered due to “auto-inflammation” is familial Mediterranean fever (FMF), also characterized by life-long bouts of fever with local and systemic inflammation, is due to a mutation in a protein. The mutation in FMF is found in the intracellular protein called pyrin (reviewed selleck screening library in 14). WT pyrin binds to ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), an essential component for the activation of caspase-1 and the processing of IL-1β. It is thought that pyrin functions to sequester ASC and prevent its participation in caspase-1 activation; however, mutated pyrin appears to lose part of the ASC binding and, as a result, there is a greater activation of caspase-1 and secretion

of IL-1β. Indeed, attacks of FMF are fully prevented by anakinra (see Table 1), although the disease is usually controlled by daily colchicine. However, in patients whose disease is poorly controlled by colchcine, blocking IL-1 rapidly returns the patient to normalcy. The attacks of FMF

are seemingly unprovoked, but it is likely that constitutional changes such as stress, viral infections or dietary components trigger the activation of caspase-1 and release of IL-1β. In 2001, Hal Hoffman described a mutation in a protein in families who experience systemic and local inflammatory responses upon exposure to cold 15. Termed familial cold auto-inflammatory syndrome (FCAS), the mutation was found to be in a protein that Hoffman named cryopyrin (now termed nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3)). Together with ASC, NLRP3 participates in the activation of caspase-1 16. Patients with FCAS Tacrolimus (FK506) are treated with anakinra or the IL-1 soluble receptor rilonacept 17. Two other diseases with mutations in NLRP3 are Muckle–Wells syndrome (MWS), which can also be triggered by exposure to cold, and chronic infantile neurological, cutaneous and articular (CINCA) syndrome (also termed neonatal onset multisystem inflammatory disease, NOMID). Together FCAS, MWS and CINCA are called cryopyrinopathy-associated periodic syndrome (CAPS) and are uniquely IL-1β-mediated diseases. The mAb to IL-1β, canakinumab, is approved for the treatment of CAPS.

Single-cell suspensions of 1 × 106 cells in a 50 μl or 100 μl of whole blood were washed with fluorescence activated cell sorter (FACS) buffer [phosphate-buffered saline (PBS) supplemented with 2% FBS and R788 ic50 0·02% sodium azide] and then preincubated with rat anti-mouse CD16/CD32 (clone 2.4G2) to block Fc binding. Specific antibodies were then added to the samples and incubated for 30 min at 4°C. Stained samples were then washed and fixed with 2% paraformaldehyde

for cell suspensions or treated with BD FACS lysing solution for whole blood. At least 50 000 events were acquired on LSRII or FACSCalibur instruments (BD Biosciences). Data analysis was performed with FlowJo (Tree Star, Inc., Ashland, OR, USA) software. Cytokine production by human CD4 and CD8 T cells selleck monoclonal humanized antibody inhibitor was quantified using the BD Cytofix/Cytoperm Kit Plus GolgiStop (BD Biosciences), according to the manufacturer’s instructions. Splenocytes were recovered from the indicated mice at 12 weeks after implant of fetal tissues. Red blood cells were lysed and 1 × 106 cells were then left unstimulated or stimulated with phorbol myristate acetate (PMA) (0·5 μg/ml) and ionomycin (0·5 μg/ml) in the presence of GolgiStopTM (0·1 μg/ml) for 4 h at 37°C in 5% CO2. Cells were then fixed and permeabilized using Cytofix/Cytoperm solution and stained with monoclonal antibodies

(mAb) to interferon (IFN)-γ (clone 4S.B3; eBioscience), IL-2 (clone MQ1-17H12; eBioscience), IL-17A (clone eBio64DEC17; eBioscience) and IL-22 (clone IL22JOP; eBioscience). Stained samples were analysed as described above. CD4+ human Treg were identified in the blood of NSG–BLT mice by staining with antibodies specific for human CD25 (clones

MA-251 and 2A3), CD127 (clone A019D5) and forkhead box protein 3 (FoxP3) (clone Adenylyl cyclase 236A/E7). For staining, 100 μl of whole blood were washed with FACS buffer and then preincubated with rat anti-mouse FcR11b. Antibodies specific for human cell surface markers (CD45, CD3, CD4, CD25 and CD127) were added to the samples and incubated for 30 min at 4°C. Stained blood samples were then treated with BD FACS lysing solution for whole blood. Cells were incubated in eBioscience fixation/permeabilization buffer for 60 min and stained with antibodies specific for human FoxP3 in eBioscience permeabilization buffer for 60 min. Stained samples were analysed as described above. Heparinized blood samples from engrafted mice were centrifuged and the plasma was stored at −80°C. Human IgM and IgG levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit (Bethyl Laboratories, Inc., Montgomery, TX, USA) according to the manufacturer’s instructions and an EMax Endpoint ELISA microplate reader (Molecular Devices, Sunnyvale, CA, USA).

aureus (Fig. 5B) and influenza virus (Fig. 5D), that is the only two microbes that promoted IL-2 and IFN-γ responses. In this study, we show that cord pDC promote a Th2 phenotype. However, the Th2-skewing effect of cord pDC could be omitted by enveloped viruses. This implies that virus can divert Th2-biased responses in human cord T

cells. Furthermore, we show that microbes capable of inducing IFN-α promote Th1 responses, whereas a microbe’s ability to induce IL-12 does not correlate to its ability to induce IL-2 or IFN-γ responses in vitro. The numbers of human studies of adaptive T cell responses in newborns compared with adults are limited and conflicting [37]. Yet, it is generally thought that the immune system of newborns is immature and differs from that in adults. The T cell polarization in newborns is correlated with impaired Th1 responses [38, 39]. buy MAPK Inhibitor Library However, individual Th1/Th2 balance in newborns varies depending on parental and environmental

factors [40]. In this paper, we show that the baseline production of the Th2 cytokines IL-5 and IL-13 were elevated in cord CD4+ T cells compared with adult T cells. The Th2 cytokine induction observed in cord cells was not an intrinsic function of the neonatal T cells, but rather a Th2-inducing effect of cord pDC. This is in line with previous Sirolimus findings where pDC was shown to promote Th2 responses in healthy and allergic subjects [15, 19]. This is, to our knowledge, the first study to show that the levels of Th2 cytokines obtained in vitro activated T cells differs between newborns and adults. We could not detect any significant differences in Th1 cytokine synthesis (IFN-γ and IL-2) between T cells from adults and newborns, even though others have shown that cord blood DC is impaired in their capacity to induce both IFN-γ and IL-2 in responding T cells

[39]. Instead, our data imply that cord pDC were superior to both cord mDC and adult DC in promoting Th2 responses. The Th2-skewing effect of cord pDC can be blocked by viral stimuli. We found that enveloped viruses (i.e. HSV-1, coronavirus, CMV, morbillivirus Cepharanthine and influenza virus) blocked IL-13 secretion, while bacteria and non-enveloped viruses did not. This confirms previous findings from us and others, showing that the Th2 skewing effect of pDC in newborns and adults can be omitted by microbial stimuli [3, 19]. However, the diminished IL-13 production that was seen in virus stimulated cultures could not be correlated with Th1 polarization, that is IFN-α, IFN-γ, IL-2 or IL-12 secretion. None of the viruses tested could induce IL-12 secretion, and influenza was the only inactivated virus to evoke IFN-α, IFN-γ and IL-2 production. Still, these findings emphasize the importance of early life microbial stimuli of the innate immune system for an accurate maturation of the immune system, that is to avoid unwanted Th2 responses.