We next conducted a cellular analysis to evaluate the degree of lymphocyte activation in both groups of disease-free mice (Fig. 3). Consistent with the adjuvanticity

of LPS, treated mice displayed overall increased lymphocyte number and activity in the spleen (Sp) and, more notably, in the lymph nodes draining the pancreas (pLN) (Fig. 3A). Gross subdivision of lineages as CD8 or CD4 T cells, B cells or Dendritic cells did not reveal preferential expansion (not shown and Fig. S2). Splenic B lymphocytes showed an activated phenotype as indicated by elevated MHC Class II expression (Fig. S2). Moreover, seric IgG and IgM titres were readily increased (not shown). Despite the systemic effect of long-term LPS treatment, effector CD4 T cells were not significantly affected as measured by the frequency of CD69+ or CD44high cells in spleen and pLN. Noteworthy, CD4+CD69+CD44hi cells, previously

described as primed cells enriched in diabetogenic PCI-32765 purchase effectors [10], were found in the spleen and pLN of both groups of mice (Figs. 3B and S3). Similarly, while T lymphocyte differentiation into IFN-γ-producing helper cells is essential for diabetes establishment in NOD mice [50], LPS-treated and healthy controls displayed similar frequency of CD4+IFN-γ+ cells in spleen and pLN (Figs. 3C and S3). Infiltration of CD4+IFN-γ+ selleck inhibitor cells was also detected in pancreas of healthy and LPS-protected animals (Fig. S3). Taken together these analyses indicate that LPS treatment while preventing

disease development did not induce immune paralysis, nor impaired Th1 differentiation, an effector class essential for diabetes establishment in NOD mice [50]. We conclude that LPS-induced protection in NOD mice, similarly to spontaneous protection, operated by a mechanism that did not impede pancreatic islet infiltration and effector CD4+ cell activation. We Sinomenine next assessed whether Treg undergo phenotypic modifications in vivo upon LPS treatment by analysing the frequency and numbers (Figs. 4, 5 and S4–S6) of specific CD4 cell subsets. Historically, Treg were first defined as CD4+CD25+ T cells [51]. Yet, activated conventional T cells also express CD25 in a transient manner upon activation. LPS treatment in NOD mice did not increase the frequency and number of CD4 cells expressing CD25 (Fig. 4A). While CD4+CD25+ cells expressing high levels of l-selectin have been shown to be particularly potent in preventing diabetes occurrence [18], the frequencies of CD62LhiCD4+CD25+ splenocytes in each experimental group were not significantly different (data not shown). CD103-expressing CD4+CD25+ cells display increased regulatory function in vivo [52, 53] and CD103 expression is likely a molecular signature of pancreatic Treg [10]. Strikingly, LPS-protected mice presented an increased frequency and number of CD103+CD4+CD25+ cells, both in the spleen and in pLN (Figs. 4B and S4), when compared with healthy controls.

“
“Foxp3+ T regulatory (Treg) cells can be induced to produce interleukin (IL)-17 by in vitro exposure to proinflammatory cytokines, selleck chemicals llc drawing into question their functional stability at sites of inflammation.

Unlike their splenic counterparts, Treg cells from the inflamed central nervous system (CNS-Treg cells) during EAE resisted conversion to IL-17 production when exposed to IL-6. We show that the highly activated phenotype of CNS-Treg cells includes elevated expression of the Th1-associated molecules CXCR3 and T-bet, but reduced expression of the IL-6 receptor α chain (CD126) and the signaling chain gp130. We found a lack of IL-6 receptor on all CNS CD4+ T cells, which was reflected by an absence of both classical and trans-IL-6 signaling in CNS CD4+ buy GSK2126458 cells, compared with their splenic counterparts. We propose that extinguished responsiveness to IL-6 (via down-regulation of CD126 and gp130) stabilizes the regulatory phenotype of activated Treg cells at sites of autoimmune inflammation. Foxp3+ Treg

cells are primary mediators of peripheral tolerance and have shown therapeutic potential in models of organ-specific autoimmune disease [[1]]. However, Treg cells have also been reported to produce interleukin (IL)-17 when stimulated in vitro in the presence of inflammatory cytokines [[2, 3]], suggesting that Treg cells can adapt to an inflammatory environment by acquiring certain effector characteristics. Here, we tested whether Treg cells isolated from a site of autoimmune inflammation could be driven toward an effector phenotype. We used the experimental autoimmune stiripentol encephalomyelitis (EAE) model wherein Foxp3+ Treg cells accumulate in the inflamed central nervous system (CNS). Unlike their splenic counterparts, CNS-Treg cells resisted conversion into an IL-17-secreting population. This resistance was attributable to a reduction in IL-6 responsiveness due to the fact that

CNS-Treg cells lacked expression of both chains of the IL-6 receptor, CD126, and gp130. We therefore reveal a key mechanism allowing Treg cells that are active in sites of inflammation to maintain a commitment to an antiinflammatory role. We fluorescence-activated cell sorter (FACS)-sorted Treg (GFP+) and non-Treg (GFP−) CD4+ cells from the spleen and CNS of Foxp3-GFP mice with EAE and assessed their cytokine production profile. CNS Foxp3− T cells showed production of IL-2 and a broad range of effector cytokines (IL-4, IL-5, IL-17, IFN-γ, TNF-α, and GM-CSF) in response to anti-CD3+anti-CD28 stimulation. In contrast, Foxp3+ cells from the CNS showed no production of these effector cytokines, with only low-level production of IL-10 being evident (Fig. 1A). We next tested FACS-sorted GFP+ (Foxp3+) CNS-Treg cells under in vitro exposure to a well-characterized IL-17-promoting cocktail.

We next examined the effect of proximal promoter deletion on ST2 expression in fibroblasts. First, we quantitated total ST2 expression using a qPCR assay that measures both ST2L and sST2. ST2 expression was abolished in promoter deficient Staurosporine cost fibroblasts compared with the high amounts of total ST2 expression seen in wild-type fibroblasts (Fig. 2A). In contrast, BMMCs from both wild type and knockout mice expressed similar amounts of ST2, consistent with the results shown in Fig. 1. We treated fibroblasts

with either PMA or PDGF, which have previously been shown to increase sST2 expression [4], however these agents induced minimal sST2 expression in the promoter-deficient fibroblasts compared with wild-type cells. These results imply that the large majority of ST2 expression in fibroblasts, even following activation, is dependent on the proximal promoter and enhancer element. Next, a series of PCR assays were performed to measure sST2 or ST2L transcripts initiated from either the distal or proximal promoter (primer locations indicated in Fig. 1A). The majority Opaganib in vitro of ST2

expression in BMMCs was linked to exon 1a of the distal promoter (both sST2 and ST2L); however, some ST2L expression was associated with the proximal promoter (Fig. 2B). In contrast, both sST2 and ST2L expression in fibroblasts were linked to the proximal promoter, either in untreated cells or following activation with serum, PMA, PDGF, or a combination of IL-17 and TNF. This was true for both primary tail-derived fibroblasts and 3T3 fibroblasts. No fibroblast expression was associated with the distal promoter, even though very low amounts of sST2 transcript could be detected in stimulated knockout fibroblasts samples (Fig. 2A and other data not shown),

suggesting there may be additional sites of ST2 RNA initiation. Interestingly, triclocarban wild-type fibroblasts expressed both sST2 and ST2L (Fig. 2B). In order to determine if fibroblasts were responsive to IL-33, we measured the gene expression of a panel of inflammatory mediators following IL-33 treatment. As shown in Fig. 2C, IL-33 stimulation for 4 h resulted in induced expression of a selective set of chemokines and cytokines in wild type, but not promoter knockout tail fibroblasts (induction of CXCL1, CXCL10, and CCL2, but not CCL27, TGF-β1, or IL-18). This observation is consistent with another report describing IL-33 activity on fibroblasts [17] and, moreover, suggests that fibroblasts are a potential source of the neutrophil-attracting chemokine CXCL1, which is induced by IL-33 in vivo [18]. We next measured the production of sST2 protein from fibroblasts. Wild-type tail fibroblasts and 3T3 fibroblasts both secreted sST2 protein in response to stimulation with either serum, PMA or IL-33 (Fig. 2D and data not shown). In contrast, knockout fibroblasts produced no sST2 protein under any of the stimulation conditions tested. The proximal promoter is thus essential for sST2 protein secretion from fibroblasts.

For instance, full length chimeric molecules containing the N-terminus and collagen domains of SP-D connected to the NCRD of conglutinin or human mannose binding lectin (MBL) have significantly greater neutralizing activity than wild-type SP-D [14, 15]. Furthermore full length trimers

of CL-43, or the CL-43 NCRD have strong antiviral activity [16]. Given that SP-D recognizes high mannose glycans associated with the viral hemagglutinin and the neuraminidase [6], our initial hypothesis was that the same structural adaptations were responsible for the enhanced recognition of mannose-rich oligosaccharides of mannan and IAV by CL-43 [16]. In this paper, we compare antiviral properties of NCRD preparations of SP-D and the serum collectins. We report for the first time strong antiviral activity of the bovine serum collectin

CL-46 NCRD. To further analyse the increased antiviral activity of bovine serum collectins Selleckchem Napabucasin we prepared novel mutant versions of hSP-D-NCRD in which specific residues found in serum collectins replace those of wild-type SP-D. These mutants were then compared for antiviral AZD4547 mw activity and binding to mannan. Finally, we determine interactions of functionally enhancing monoclonal antibodies raised against SP-D with bovine collectin NCRD. Virus preparations.  Influenza A virus was grown in the chorioallantoic fluid of 10-day-old chicken eggs and purified on a discontinuous sucrose gradient as previously described [17]. The virus was dialysed against PBS to remove sucrose, aliquoted and stored at −80 °C until needed. Philippines 82/H3N2 (Phil82) and Brazil78/H1N1 (Braz78) strains and their bovine serum inhibitor resistant variants, Phil82/BS and Braz78/BS, were kindly provided by Dr. E. Margot Anders (University of Melbourne, Melbourne, Australia) [18]. Post-thawing the viral stocks contained approximately 5 × 108 plaque forming units/ml. Collectin preparations.  PAK6 Dodecamers of wild-type recombinant human SP-D were used as control and were expressed in CHO cells and purified as described [19]. Trimeric NCRD fusion proteins, including the wild-type human and rat NCRD (hereafter, called

hSP-D-NCRD and rNCRD, respectively), mutant constructs of the hSP-D-NCRD and rNCRD, and NCRD of other collectins (apart from that of CL-46) were produced in E. coli as described [20, 21]. All fusion proteins contain an identical N-terminal His-tag that facilitates purification. An internal S-protein binding site permits detection using S-protein horseradish peroxidase (HRP), as previously described [21]. All NCRD migrated as a single major band of the appropriate size for trimers on SDS–PAGE with the expected decrease in mobility on reduction, consistent with the formation of normal intrachain disulphide bonds. All showed retention of some or all of the calcium-dependent carbohydrate binding activities of the native protein.

Lysosomal storage disorders result from inherited defects in lysosomal proteins [10]. These disorders can be caused either by a primary defect in a catabolic Veliparib molecular weight enzyme (e.g. Tay-Sachs and Sandhoff disease) or a defect in a transporter, channel or regulatory protein (e.g. Niemann-Pick type C (NPC1) disease). Lysosomal storage caused by a deficient lysosomal enzyme has been shown to lead to reduced iNKT cells in murine models of Sandhoff disease [11, 12], Tay-Sachs disease [11], GM1 gangliosidosis

[11-13] and Fabry disease [14, 15]. In the NPC1 mouse the numbers of iNKT cells also are greatly reduced but this is associated with impaired late-endosome/lysosome fusion in addition to the lysosomal lipid storage [11, 16]. NPC disease can be caused by mutations in one of two genes NPC1 or NPC2 [17]. Dysfunction of the NPC1 protein leads to decreased lysosomal calcium content which accounts for the failure of endocytic vesicle fusion and the complex pattern of lipid storage observed [18]. With the differential trafficking of murine and human CD1d for iNKT-cell

ligand selleck products presentation ex vivo and the requirement of normal lysosomal CD1d trafficking/function for murine iNKT-cell development in vivo, we reasoned that examining iNKT cells in NPC patients would reveal whether the findings in the murine model extends to humans. It has been reported that iNKT cells are present at normal frequencies in the peripheral blood of Fabry disease patients [19] and are slightly increased in Gaucher disease patients [20]. Here, we have studied iNKT-cell frequencies and functional responses

in NPC1 disease patients and the ability of patient-derived EBV-B-cell lines to stimulate iNKT cells. In contrast to the murine model of NPC1, we found unchanged iNKT-cell frequencies in NPC1 patients. In addition, the functional response of NPC1 iNKT cells to stimulation was normal, as was the ability of NPC1 antigen presenting cells to present a variety of iNKT cells ligands to control iNKT cells. We analysed the frequency of iNKT Lonafarnib in vivo cells in the peripheral blood of controls, NPC1 patients and NPC1 heterozygote carriers by flow cytometry (gating strategy, Supporting Information Fig. 1). As previously reported [21], the frequencies of iNKT cells are very low in normal human peripheral blood, typically in the range of 0.1–1% of total T cells (Fig. 1A). In contrast to the NPC1 mouse where iNKT cells are undetectable, iNKT cells could be identified and were present at normal frequencies in the peripheral blood of NPC1 patients and heterozygotes (Fig. 1A). This indicates that fusion of late endosomes and lysosomes is not required for the generation, delivery or loading of iNKT-cell selecting ligand(s) in the thymus or for their maintenance in the periphery.

Thus, anti-HLA class II antibody was seen in a total of 48 samples (72%). Of the 55 samples with anti-HLA antibodies, the antibodies check details were donor-specific anti-HLA antibodies (DSA)

in 33 samples (49%), including class I antibody alone in two samples (3%), class II antibody alone in 27 samples (40%), and both class I and II antibodies in four samples (6%) (Table 4). Thus, class II DSA antibody was seen in a total of 31 samples (46%). de novo DSA was detected in 10 samples (15%), including class I antibody alone in two samples (3%), and class II antibody alone in eight samples (12%). Among our study, 22 BS (26%) met all the criteria for c-AMR in the Banff ’09 classification, including TG, C4d deposition in the PTC and presence of DSA, while 27 BS were diagnosed

as suspicious of c-AMR. The prognoses of the patients with TG are shown in Table 5. Eleven cases lost their graft during the observation period. Three patients were dead with a functioning graft. Of the other cases with functioning grafts, deterioration of the renal allograft function after the biopsies was seen in 20 patients (40%). TG is a pathologic condition of renal allografts Adriamycin datasheet that was recognized more than four decades ago.[5] TG has been widely recognized as a pathological change of chronic rejection. TG is included as a criterion of chronic allograft nephropathy (CAN) with chronic rejection in the Banff 97 classification, and of c-AMR in the Banff 05, 07 and ‘09 classifications.[2, 3, 6, 7] The risk Baf-A1 in vitro of TG is higher in patients with a history of AMR. Sis et al. reported a high incidence

of previous rejection (54%), in their clinically indicated biopsy study.[8] Other studies have reported that approximately 45% of patients with a-AMR later developed TG as compared with 6% of recipients without rejection.[9, 10] In our study, 42 of the 50 patients (84%) had experienced rejection episodes prior to this study, of which 30 (60%) patients had experienced a-AMR episodes; in the latter patients, the a-AMR might have progressed to TG. The clinical manifestations of transplant glomerulopathy include progressive loss of kidney allograft function and proteinuria.[1] In the earlier stages, the patients may have mild sub-nephrotic-range proteinuria and unexplained mild deterioration of graft function.[1] Proteinuria of more than 1+ by dipstick test was present in 27 of the 50 patients (54%) in our study. The median serum creatinine level at the time of the allograft biopsy was not very high, being 1.77 mg/dL. Based on these findings, we consider that some of our patients had subclinical TG. In this study, TG was characterized mainly by peritubular capillaritis (86%), followed in frequency by transplant glomerulitis (76%) and IF/TA (83%). Thickening of the basement membrane of the PTC (ptcbm) was also found in 71% of cases.

Candida colonisation was found in 4.6% of neonates and the only Candida species isolated was C. albicans. The rectal mucosa was significantly more colonised than oral mucosa. It is known that Candida colonises the gastrointestinal tract of 4.8–10% neonates and that C. albicans is the predominant species,[13] but not much is known about the process of the oral and rectal colonisation.[11, 16-18] Oral colonisation seems

to increased from birth up to the 18th month of age and then decreased.[11] Rectal colonisation seems to be more frequent.[16, 17] Our findings, derived from MG-132 cost swabbing very early in life, do not confirm the hypothesis that the earliest site colonised is the oral cavity.[18] These AZD1208 concentration differences may be attributed to different study design and setting as well as to the age of sampling. In this study, neonates were only colonised by C. albicans, which is observed mainly in vertical transmission, whereas C. parapsilosis has been observed in horizontal

transmission in the neonatal intensive care unit setting.[19] It is of great interest that all non-colonised mothers gave birth to non-colonised neonates, that all colonised neonates were born from colonised mothers and furthermore that C. albicans was the only species isolated from 16 mother–infant pairs. The molecular typing study showed that in all colonised neonates the pulsotype of C. albicans was identical to the pulsotype of their mothers. According to PFGE-BssHII typing method, the 16 maternal C. albicans isolates were different. Electrophoretic karyotyping of the maternal C. albicans isolates displayed seven isolates with identical bands suggesting clonal relatedness. However, this method has a less discriminatory power than PFGE-BssHII.[9] These findings suggest that colonised neonates may acquire C. albicans via vertical transmission. These C. albicans colonised neonates met criteria for vertical transmission according to the research of Bliss et al. [4] had been born by C. albicans colonised mother, developed C. albicans colonisation Chlormezanone by 1 week of age and had C. albicans isolate identical to the maternal isolate. All colonised neonates

were full term and healthy, except for one of vaginal delivery with oral colonisation, who was admitted to Neonatal Intensive Care Unit because of respiratory distress. It is interesting that neonatal Candida colonisation is mostly investigated among preterm neonates in Neonatal Intensive Care Units, where horizontal transmission may be more possible; Bliss et al. [4] demonstrated that 41% of C. albicans colonising very low-birthweight infants was due to vertical transmission; Waggoner-Fountain et al. [5] demonstrated that 14% of mother–preterm infant pairs were colonised with the identical strain of C. albicans. According to Caramalac et al. [11] vaginal mucosa was not the main route of Candida transmission to full-term neonates.

(B) Both cska and non-cska-TCRs are degraded in the lysosome following activation. Splenocytes, were non-activated or activated as in (A), in the absence or presence of the lysosomal inhibitor NH 4 Cl, lysed and processed as in (A) for detection of ζ and ZAP-70. (C) Accumulation of cska ζ in activated T-cells following treatment

with NH 4 Cl. Average values and standard deviation were determined from six independent experiments, using ζ expression level of non-activated, NH 4 Cl untreated samples as 100%. Figure S8. FACS gateing strategy. Vemurafenib order In all the FACS results presented in the paper, the first gate distinguished between live and dead/debreas cells (A). The cells were stained using anti-Thy 1.2 antibodies, which enabeled us to focuse on the T cells by gating on the positive population or on the APCs (LK cells in the mixed experiment) by focusing on the negetive population (B). The result was obtained by integreating gate 1 and gate 2 as in the presented sample presented (C). “
“Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease of hematopoietic stem cells. The disease progresses after several years from an initial chronic phase to a blast phase. Leukemia-specific T cells are regularly detected in CML patients and may be involved in the immunological control of the

disease. Here, we analyzed the role click here of leukemia-specific CD8+ T cells in CML disease control and the mechanism that maintains CD8+ T-cell immunosurveillance in a retroviral-induced murine

CML model. To study antigen-specific immune responses, the glycoprotein of the lymphocytic choriomeningitis virus was used as model leukemia antigen. Leukemia-specific CTL activity was detectable in vivo in CML mice and depletion of CD8+ T cells rapidly led to disease progression. CML-specific CTL were characterized by the expression of the IL-7 receptor PAK5 α-chain. In addition, leukemia cells produced IL-7 that was crucial for the maintenance of leukemia-specific CTL and for disease control. Therefore, CML cells maintain the specific CD8+ T-cell-mediated immune control by IL-7 secretion. This results in prolonged control of disease and probably contributes to the characteristic chronic phase of the disease. Chronic myelogenous leukemia (CML) is a malignant clonal disease originating from a pluripotent hematopoietic stem cell expressing the reciprocal translocation t(9;22), which forms the oncogenic BCR/ABL fusion protein. BCR/ABL is a constitutively activated tyrosine kinase which plays a critical role in the pathogenesis of CML. After several years and acquisition of a second genetic abnormality, the disease progresses from the chronic phase to terminal blast phase in which the patients develop an acute leukemia of either myeloid (AML) or, less frequent, lymphoid (ALL) cell type 1–3. For unknown reasons, CML seems to be the most immunogenic leukemia.

The modalities of this tolerance induction might be considered as mirroring innate immunity and so be described as ‘innate tolerance’. CD1d-restricted immune responses should also be considered within such a group of tolerance effectors. CD1d is a non-classical major histocompatibility class 1-like molecule that primarily presents either find more microbial or endogenous glycolipid antigens to T cells involved in innate immunity. CD1d-restricted T cells comprise NKT cells and a subpopulation of γδ T cells expressing the Vγ4 T-cell receptor. In particular, activated NKT cells secrete large quantities

of cytokines that both help control infection and modulate the developing adaptive immune response. However, NKT cells can also promote Treg-cell activation[75] and the chronic in vivo stimulation of NKT often leads to a Th2 bias in the immune response and promotes the generation of tolerogenic dendritic cells. Selleckchem AP24534 Furthermore, with similar modalities to MSC and macrophages, reagents have been identified that, by interacting with CD1d, differently bias Th-cell

responses.[76] One of the best examples in which effectors of such ‘innate tolerance’ are actively recruited is cancer. Tumour cells evade immune system recognition not only by mutating antigenic epitopes initially recognized by host immune surveillance, but also and especially by creating an environment that is extremely potent at inhibiting immune responses in a non-specific fashion. Fibroblasts[77] and immunosuppressive myelomonocytic cells[78] heavily infiltrate the tumour process and facilitate the activation of ‘adaptive tolerance’ effectors like Treg cells.[45] Within this context, it is plausible to surmise a major role of MSC because of their

ability to polarize and activate Thymidine kinase immunosuppressive networks as summarized in this review. This hypothesis gains support also by a recent set of data elegantly generated using a transgenic mouse in which stromal cells could be depleted. The depletion of cells expressing fibroblast activation protein-α caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumours by a process involving IFN-γ and TNF-α.[79] Mesenchymal stromal cells can also contribute to the tumour-related immune impairment because they produce TGF-β, which can suppress or alter the activation, maturation and differentiation of both innate and adaptive immune cells.[80] In addition, TGF-β has an important role in the differentiation and induction of Treg cells. Furthermore, in the presence of IL-6, also produced by MSC, TGF-β induces the differentiation of IL-17-producing CD4+ Th17 cells, which may have tumour-promoting activities.[81] An interesting proposal for a ‘tissue-based’ approach to the regulation of the immune response has been recently put forward by Matzinger and Kamala.

These observations let the authors conclude that the presence of cord blood IgE was, in the majority of cases, a result of maternal transfer. Our results PI3K inhibitor showed a strong correlation between cord blood anti-Der p IgG, IgG1, IgG2 and IgG4 and respective maternal levels. Although we do not have data on IgG levels in children at 6 months of age, our data suggest a maternal transfer of anti-Der p IgG subclasses

across placenta. In addition, the decreased ratio of cord blood to maternal levels of these antibodies at high maternal concentrations suggests a saturable receptor-mediated transfer. Notably, the syncytiotrophoblast expresses a neonatal Fc receptor (FcRn) that is essential for IgG transfer [3, 39] and is saturable [40]. This receptor has a higher affinity for IgG1, compared to other IgG subclasses, which may explain the more efficient in utero transfer of Der p-specific IgG1, compared to other subclasses [3], as also shown here. Several studies in rodents have reported that maternal allergen-specific IgG inhibits allergic responses in the offspring [2, 9–16]. Proposed mechanisms of protection by maternal IgG include the following: (1) IgG binding to allergen, leading to allergenic determinant masking and clearance of the immune complexes by phagocytosis,

(2) IgG blockade of IgE binding to allergen and hence inhibition of mast cell degranulation and (3) interactions with inhibitory receptor FcγRIIb on neonatal B lymphocytes or dendritic cells [2, 41]. More recently, protection from allergic airway disease Clomifene by antigen transfer Selleck Temsirolimus through breast milk was shown to be more stronger and of longer duration when maternal allergen-specific IgG is present in breast milk. The authors attributed the increased protection to the formation of allergen–IgG immune complexes that are easily transferred across the neonatal gut barrier compared to uncomplexed antigen and display tolerogenic properties [42]. Human studies also suggest an immunoregulatory role for in utero transfer of maternal IgG. A study by Glovsky et al. [43] analysed the effect of specific immunotherapy during pregnancy on allergic sensitization in

children. Their data suggested that blocking antibodies induced by immunotherapy were transferred across the placenta and were responsible for decreased allergic sensitization in their children. Jenmalm and Bjorkstén [21] found that high concentration of IgG directed to inhaled allergens in cord blood was associated with reduced atopy in children. Another study showed a transient protective effect of placental transfer of maternal antibodies on allergic immune response [22]. The current study demonstrated a higher concentration of specific IgG4 and, to a lesser extent, of IgG2 in cord blood of neonates from atopic mothers compared to non-atopic mothers. Although we cannot conclude that these IgG subclasses exert an immunoregulatory role, a protective effect has previously been reported for IgG4 [44–46].