On day 7, the cells were harvested for injection, 5 × 106 cells were suspended in 5 ml normal saline containing 1% autologous plasma, mixed with absorbable gelatin sponge (Gelfoam; Pharmacia & Upjohn, Peapack, NJ, USA) and

infused through an arterial catheter following Lipiodol (iodized oil) (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) injection during selective TAE therapy. Release criteria for DCs were viability > 80%, purity > 30%, negative Gram stain and endotoxin polymerase chain reaction (PCR) and negative c-Met inhibitor in process cultures from samples sent 48 h before release. All products met all release criteria, and the DCs had a typical phenotype of CD14- and human leucocyte antigen (HLA)-DR+. Epigenetics inhibitor The DC preparation was assessed by staining with the following monoclonal antibodies for 30 min on ice: anti-lineage cocktail 1 (lin-1; CD3, CD14, CD16, CD19, CD20 and CD56)-fluorescein isothiocyanate (FITC), anti-HLA-DR-peridinin chlorophyll protein

(PerCP) (L243), anti-CCR7-phycoerythrin (PE) (3D12) (BD PharMingen, San Diego, CA, USA), anti-CD80-PE (MAB104), anti-CD83-PE (HB15a) and anti-CD86-PE (HA5.2B7) (Beckman Coulter, Fullerton, CA, USA). Cells were analysed on a fluorescence activated cell sorter (FACS0CaliburTM flow cytometer. Data analysis was performed with CELLQuestTM software (Becton Dickinson, San Jose, CA, USA). Immature DCs and OK432-stimulated DCs were incubated with 1 mg/ml FITC dextran (Sigma-Aldrich,

St Louis, MO, USA) for 30 min at 37°C and the cells were washed three times in FACS buffer before cell acquisition using a FACSCaliburTM cytometer. Control DCs (not incubated with FITC dextran) were acquired at the same time to allow background levels of fluorescence to be determined. DCs were seeded at 200 000 cells/ml, and supernatant collected after 48 h. IL-12p40 and IFN-γ were detected using matched paired antibodies (BD Pharmingen) following standard protocols. The ability of DCs to exert cytotoxicity was assessed in a standard 51Cr release assay [19]. We used the HCC heptaminol cell lines Hep3B and PLC/PRF/5 [American Type Culture Collection (ATCC), Manassas, VA, USA] and a lymphoblastoid cell line T2 that expresses HLA-A*0201 (ATCC) as target cells. Target cells were labelled with 51Cr. In a 96-well plate, 2·5 × 103 target cells per well were incubated with DCs for 8 h at different effector/target (E/T) ratios in triplicate. Percentage of specific lysis was calculated as follows: (experimental release − spontaneous release)/(maximum release −  spontaneous release) × 100. Spontaneous release was always < 20% of the total.

Despite initially encouraging data from preclinical and clinical studies, the efficacy of human adenoviral vector serotype

5 (AdHu5) was hampered by a strong pre-existing anti-vector immunity among vaccinated macaques, in which transgene-specific T cells homed to different organs in the presence of anti-vector immunity.140Listeria monocytogenes is known to induce strong cellular immune responses. Listeria monocytogenes induces multiple effector mechanisms, including antigen presentation via MHC class I and II pathways as well as induction of innate immune responses.141 As L. monocytogenes is a ubiquitous bacterium, anti- L. monocytogenes immune responses are likely to be https://www.selleckchem.com/products/jq1.html present among the majority of individuals. Sciaranghella et al.142 constructed a live-attenuated L. monocytogenes MK-8669 vector, which encodes SIVmac239 gag. The novel, live-attenuated L. monocytogenes vector may be an attractive

platform for oral vaccine delivery. Although HCV leads to impairment of both MDC and PDC according to many researchers, the mechanisms how HCV affects DC function remains elusive.55 Further research is needed in regard to the mechanisms of HCV-induced DC impairment and the correlation between DC function and HCV persistence. Dendritic cell-based vaccination/therapeutic approaches are safe and promising in terms of their propensity to establish anti-HCV adaptive immune responses. However, possible side-effects of DC-based therapeutic vaccine should be carefully evaluated, especially those possibly inducing

a strong T-cell-mediated immunity, because of the dual role of virus-specific cytotoxic T cells mediating both viral clearance and tissue Janus kinase (JAK) damage. Nevertheless, the achievements in this field of studies brought us the hope of opening new routes to the prevention and treatment of HCV infection. Prospects of a DC-based vaccine against HCV infection include employment of adjuvants, the blockage of negative regulatory signal and enhancement of positive regulatory signals, so as to improve the vaccine immune response against HCV infection, reduce HCV viral load, and hinder progression of chronic liver disease. This work is supported by the National High Technology Research and Development Program of China (No. 2007AA02Z441, 863 Program) and the National Natural Science Foundation of China (No.31170877 and No.81170389). No conflicting financial interests exist. “
“IL-17-producing CD4+ T cells (Th17) have been classified as a new T helper cell subset. Using an IL-17 fate mapping mouse strain, which genetically fixes the memory of IL-17 expression, we demonstrate that IL-17A/F-expressing T helper cells generated either in vitro or in vivo are not a stable T-cell subset. Upon adoptive transfer of IL-17F-reporter-positive Th17 cells to RAG-deficient or WT animals, encephalitogenic Th17 cells partially lose IL-17 expression and upregulate IFN-γ.

Work comparing CVID patients with a cohort of healthy controls showed only minor differences in CD20+CD27+CD43lo–int cell numbers when existing CD27+ B cell deficiencies were taken into account. Further work including absolute cell count measurements and functional assays is required with CVID patients to ascertain what role, if any, this B cell subset plays

in the pathogenesis of this disease. We would like to thank the patients and controls for their time and generosity. We would also like to thank staff members BVD-523 cost of the Clinical Immunology Laboratory for their help in this study. There are no disclosures associated with this work. “
“Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc–mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc

patients and 10 healthy controls (HC). Senescence RG 7204 was evaluated by assessing cell cycle, β-galactosidase (β-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4+ cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc–MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0–G1 phase, without significant differences between SSc and HC. SSc–MSCs showed an increased positive β-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, β-Gal staining increased significantly in SSc–MSCs. On the contrary, doxorubicin abolished

p21 activation and elicited p53 induction both in SSc– and HC–MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-β-related transcripts and their protein levels were significantly higher in SSc–MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells, www.selleck.co.jp/products/Rapamycin.html increasing surface expression of CD69 and restoring the regulatory function which is impaired in SSc. Increased activation of the IL-6 pathway observed in our cells might represent an adaptive mechanism to senescence, but preserving some specific cellular functions, including immunosuppression. Several studies have shown that mesenchymal stem cells (MSCs) represent an attractive option for new therapeutic biological approaches of autoimmune diseases, due to their plasticity, multi-differentiative potential and immunosuppressive function [1-3].

Efforts of several research groups have been combined to identify the clinical[18-20] and molecular[21-24] Alvelestat mouse parameters that are associated with an insufficient

clinical response to RTX treatment. Our group has recently found a positive association between the presence of Epstein–Barr virus (EBV) genome in the BM of patients with RA and clinical response to RTX treatment.[25] Interestingly, RTX treatment was followed by complete clearance of EBV from the BM. The ability to respond to interferon stimulation, an essential mechanism of human anti-viral defence, may potentially predict clinical effect of RTX in patients with RA.[26, 27] Infection with EBV is one of the environmental risk factors for the development of RA.[28] The EBV glycoprotein gp110 contains a sequence identical to the motif of the HLA-DRB1 alleles within the MHC II complex; called ‘shared epitope’, it is the strongest known genetic factor for the development of RA.[29-31] Also, EBV infection in carriers of shared epitope greatly enhanced the development of RA.[30] Consequently, a compromised innate immune response towards PF-02341066 in vitro EBV and poor viral clearance are attributed

to RA patients and lead to a high load of EBV-infected cells in the circulating blood and in the synovial cells, impaired cytolytic activity of T cells to EBV proteins and high titres of anti-EBV antibodies compared with healthy subjects.[32-37] B cells are currently considered critical for the primary EBV infection and for its persistence. Epstein–Barr virus activates B cells and induces their proliferation and transformation into antibody-secreting cells.[38] It has the ability to infect almost all types of B cells in vivo but naive IgM+ IgD+ B cells are the major

target in tonsils, while the latent infection is found in the memory B-cell pool.[39-41] The naive B-cell subset seems to be the cell population that shares susceptibility to RTX and EBV, so we attempted to outline phenotypic and functional changes in the peripheral blood and bone marrow B cells of patients with RA following RTX Osimertinib chemical structure treatment and during EBV infection. Samples of BM and PB were collected from 35 patients with established RA, diagnosed according to the ACR 1987 criteria[42] before B-cell depletion therapy with anti-CD20 antibodies.[13] All patients were recruited from the Rheumatology Clinic at Sahlgrenska University Hospital, Göteborg, Sweden, during the period from January 2007 to September 2008, and all patients gave written informed consent to participate. Additionally, 18 patients with RA donated PB samples for functional analysis. Another 10 patients with RA also donated PB and synovial fluids for phenotypic B-cell analysis. All patients with RA were receiving methotrexate treatment and had not been treated with RTX previously. Clinical and demographic characteristics of the patients and their immunosuppressive treatment are presented in Table 1.

“
“Citation Lin Y-S, Tsai S-J, Lin M-W, Yang C-T, Huang M-F, Wu M-H. Interleukin-6 as an early chronic inflammatory marker in polycystic ovary syndrome with insulin receptor substrate-2 polymorphism. Am J Reprod Immunol 2011; 66: 527–533 Problem  Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder. This study was to evaluate whether insulin receptor substrate (IRS)-2 Gly1057Asp polymorphism influences chronic inflammatory parameters in Taiwanese patients with PCOS. Method of

study  DNA was extracted from whole blood samples for genotyping and detection of IRS-2 Gly1057Asp polymorphism in 129 PCOS women and 109 control women. CAL-101 price Ninety-seven PCOS women accepted metformin treatment for 3 months, and low-grade chronic inflammatory markers were assessed. Results  Selleckchem Y 27632 The

levels of IL-6 were significantly elevated in PCOS women compared with normal women. Among allelic variant of IRS-2, concentrations of IL-6 were greater in IRS-2 homozygous Asp population. Treatment with metformin significantly reduced IL-6, especially in PCOS patients with IRS-2 homozygous Asp variant. Conclusion  The results showed that IL-6 may be an early low-grade chronic inflammatory marker among PCOS patients with IRS-2 polymorphism in Taiwanese population. This pharmacologic study in IRS-2 polymorphism may provide more information Baf-A1 research buy for preventing long-term complications in PCOS. “
“Pyriproxyfen is a juvenile hormone mimic of vital importance for insect development with little risk to humans. This study was performed to investigate whether large doses of pyriproxyfen affect the immune response in mammals. Mice were immunized thrice with ovalbumin in 5% ethanol, with or without pyriproxyfen or alum. Large doses of pyriproxyfen (9 or 15 mM) significantly enhanced specific total IgG immune response. This enhancement was no longer present 24 hr after treatment with

pyriproxyfen. These results suggest that pyriproxyfen is a safe chemical. Moreover, pyriproxyfen induced higher titers of IgG2a and enhanced tumor necrosis factor-alpha and gamma-interferon responses whereas alum induced IgG1 with enhanced interleukin-4 and -10. These observations indicate that the mechanism of immune enhancement by pyriproxyfen may differ from that of alum. Juvenile hormones are a group of sesquiterpenes that regulate diverse aspects of insect physiology and ensure the growth and development of larvae while preventing metamorphosis [1]. Several JHAs that are stable in the environment and mimic the biological action of JH as insect growth regulators, including methoprene, fenoxycarb and pyriproxyfen, have been synthesized [2]. Although the mechanisms of action of JHs remain unclear, the lipophilic nature of sesquiterpene JHs suggests an intracellular receptor-mediated action.

There was also no significant difference in IL-8 or TNFα responses to 0–3 h RP between infected and co-infected subjects (IL-8 Z: −0·717, P = 0·473, Figure 1a; TNFα Z: −1·050, P = 0·294, Figure 1b). In contrast to the production of IL-8 and TNFα, 0–3 h RP induced significantly elevated quantities of IL-10 by WB cultures in co-infected subjects (median: 327·4 ng/mL, range: 1124·3) compared with uninfected controls (median: 137·5 ng/mL, range: 486·3; Z: −2·063, P = 0·039; Figure 1c).

The median concentration of IL-10 production in response to 0–3 h RP was also higher in WB from infected (i.e. only positive for S. mansoni) participants (median: 190·7 ng/mL, range: 642·4, Figure 1c) compared

with uninfected controls but this trend did not reach statistical selleck chemicals llc significance (Z: −1·504, P = 0·133, Figure 1c). There was also no significant difference in 0–3 h RP-specific IL-10 secretion between the infected and co-infected groups (Z: −0·436, P = 0·451, PLX4032 research buy Figure 1c). The control stimulant zymosan induced levels of IL-10, which did not significantly differ between the three groups (Figure 1c). Further analysis of the 0–3 h RP-specific ratio of IL-10 to TNFα revealed that there was a significant increase in the cytokine ratio in response to 0–3 h RP in co-infected subjects (median: 0·039, range: 0·116; Z: −2·800, P = 0·005, Figure 2) compared with uninfected subjects (median: 0·016, range: 0·139). There was no significant difference between the zymosan-specific IL-10 to TNFα ratio in the different groups. These observations reinforce the theory that 0–3 h RP has ‘regulatory’ activity and promotes IL-10 production compared with pro-inflammatory TNFα in schistosome-infected individuals. As cytokine production is likely to be dependent upon the constituent leucocytes in the WB samples, various leucocyte Amobarbital classes were enumerated as a proportion of the total leucocyte count in the three infection groups

(uninfected n = 11, S. mansoni single infected n = 11 and co-infected n = 17; Figure 3). Eosinophils were the only leucocyte subset that was significantly affected by infection status (Kruskal–Wallis test, χ2 = 8·375, P = 0·015) with a higher percentage of eosinophils in WB from S. mansoni-infected (median: 10·6%, range: 34·2, Z: −2·331, P = 0·020) and co-infected participants (median: 12·0%, range: 43·2, Z: −2·658, P = 0·008) than in WB collected from uninfected participants (median: 4·7%, range: 20·6). There was no significant difference between the percentage of circulating eosinophils in blood collected from infected and co-infected participants (Z: −0·470, P = 0·638).

[25, 26] Candida spp., especially C. albicans, are able to produce and secrete various hydrolytic enzymes, particularly proteinases, lipases and phospholipases.[21] Shimizu et al. [27] and Abu-Elteen et al. [28] demonstrated the relevance of proteinases, hyaluronidases, condroitinases and phospholipases as virulence–related factors, reporting that secretory strains of Candida spp. showed an increased ability to invade tissues compared to non-secretory strains. According to Costa et al. [29], the activity of

proteinases and phospholipases is directly related to the promotion and establishment of infection. According to studies by Noumi et al. [30], hydrolytic enzymes and adhesins produced by C. albicans present themselves as the largest factor RAD001 research buy associated with virulence, a fact previously suggested by Neugnot et al. [31]. Secreted aspartic proteinase (Sap) was first described in 1965 and was named Candida acid proteinase due to its optimal activity at acidic pH ranges and

because it was primarily found in yeast of the genus Candida.[32, 33] Sap may be considered selleck chemical the most important hydrolytic enzyme among the virulence-associated factors of Candida spp.[34] Saps are believed to contribute to the adhesion and invasion of host tissues through the degradation or distortion of cell surface structures or the destruction of cells and molecules of the immune system, to avoid or resist microbicidal attack.[35, 36] Saps have a broad substrate specificity and are able to degrade a variety of human proteins such as albumin, haemoglobin, keratin, collagen, laminin, fibronectin, mucin and almost all immunoglobulins, including immunoglobulin A, which is resistant to the majority of bacterial proteinases.[37]

Basically, these enzymes are involved in the digestion of proteins by providing nitrogen to aid the survival of fungal cells.[38] At first glance, they appear to be acquiring nutrients; however, Saps may have developed other functions related to virulence such as degrading structural proteins Dynein and proteins of the immune system.[20, 21] In C. albicans, the production of Sap is encoded by a family of 10 SAP genes that are grouped into six subgroups or subfamilies: SAP1-3, SAP4-6, SAP7, SAP8, SAP9 and SAP10.[39-41] Gene transcription generates isoenzymes, named due to conformational and structural similarities among them.[40, 41] Sap1–Sap3 share 67% genetic identity and Sap4–Sap6 share as much as 89% identity. Sap1–Sap3 and Sap4–Sap6 are closely clustered. Sap7 only shares 20–27% identity with the other Sap proteins and is externally positioned. Sap8 is related to the clusters formed by Sap1–Sap3 and Sap4–Sap6. Sap9 and Sap10 differ from the other Sap1–8 isoenzymes and constitute a distinct group (Fig. 1).[42-44] All members of the family of Sap proteins possess four cysteine residues and two conserved aspartate residues.

Lysis of the cells was performed on ice for 30 min in 50 mm Tris–HCl, pH 7·5, containing 150 mm NaCl, 0·5 mm EDTA, 0·5% Nonidet P-40, 1 mm PMSF, 1 μg/ml aprotinin, 0·5 μg/ml pepstatin, 1·25 μg/ml leupeptin Roscovitine mouse and 1 mm dithiothreitol. After centrifugation (10 000 g, 10 min at 4°), 30 μg protein lysate supernatants were incubated in 100 μl lysis buffer with 40 μm substrate (final concentration) in microtitre plate wells at room temperature, and the increase of fluorescence due to the release of AMC was detected at 460 nm, using a 355-nm excitation wavelength in a Wallac 1420 Victor2 fluorimeter-luminometer (Wallac Oy, Turku,

Finland). The concentrations of secreted IL-1β in the cell culture supernatants after the indicated times of treatments were measured

by ELISA (BD Biosciences, San Diego, CA) according to the manufacturer’s instructions. Detection limit of the assay was 10 pg/ml. Significance of the differences between mean values was evaluated using a Student’s t-test. Data presented as mean ± SD values. To determine the effect of RWE on IL-1β production, THP-1 macrophages were treated with different combinations this website of RWE, NADPH and LPS. Although in good agreement with previous findings,[19] LPS treatment resulted in a substantial increase of the secreted IL-1β, the treatment with RWE in the absence or presence of NADPH did not trigger the secretion of this cytokine, nor did NADPH alone (Fig. 1a). However, RWE in the presence of NADPH strongly enhanced the LPS-induced IL-1β production in a dose-dependent manner at the lowest saturating LPS concentration (100 ng/ml) (Fig. 1a). A similar induction was observed at an even 10-fold higher LPS Decitabine purchase concentration and the substantial dose-dependent elevation required 24 hr after treatment (data not shown). Treatment of human monocyte-derived macrophages and dendritic cells with LPS alone or in combination with RWE led to results similar to those found with the THP-1 cell line (Fig. 1b). Pollen extract has been reported to stimulate ROS production in epithelial cells, for this reason we aimed

to see if pollen extract could induce ROS production in THP-1 macrophages. H2O2, used as a positive control, induced a fast increase in intracellular ROS (Fig. 2a). Whereas RWE but not NADPH alone induced some ROS production, their combined effect yielded a continuously increasing ROS level (Fig. 2a). Lipopolysaccharide alone did not produce detectable ROS by this method, in good agreement with previous findings,[20] nor did it enhance the ROS produced by RWE treatment in the presence of NADPH (Fig. 2a). To determine whether the RWE-dependent enhancement of LPS-induced IL-1β production is mediated by ROS, THP-1 macrophages were pre-treated with the ROS-scavenger NAC. NAC completely inhibited IL-1β secretion, indicating that ROS play an indispensable role in LPS-induced as well as in RWE-enhanced IL-1β production (Fig. 2b).

Hence, the promotion of both the adaptive and innate arms of host immunity may be highly useful towards the complete elimination of tumour cells [67,68]. Hence, the notion that immune effectors may be important for the both the genesis and therapy of tumours is based https://www.selleckchem.com/products/Bortezomib.html upon extensive previous findings. Less clear is whether oncogene inactivation specifically mediates tumour regression through immune-dependent mechanisms. Recently, CD4+ T cells have been implicated in the mechanism of tumour regression upon

inactivation in mouse models of MYC- or BCR-ABL-induced haematopoietic tumorigenesis [69]. Oncogene inactivation in MYC-induced tumours in severely immunodeficient mice resulted in significantly delayed kinetics of tumour regression and failed to eradicate tumour cells completely, leaving up to 1000-fold more minimal residual disease (MRD) than in wild-type hosts. Thus, oncogene addiction appears to comprise both cell-autonomous and non-cell-autonomous mechanisms (see Fig. 1a,b) [69]. CD4+ T cells, and not the https://www.selleckchem.com/products/PF-2341066.html canonical anti-tumour cytotoxic CD8+ T cells, emerged as the key immune effectors of sustained tumour regression upon MYC inactivation. CD4+ T cells trafficked to sites of tumour involvement as early as 4 days after MYC inactivation and persisted for up to 3 weeks. Importantly,

other effectors are also recruited to the tumour site, suggesting their possible contribution [70]. CD4+ T cells contributed to oncogene addiction by enforcing both the induction of cellular senescence and the suppression of angiogenesis [69], processes characterized previously as hallmarks of oncogene addiction (see Fig. 2). The mechanistic basis is not entirely clear, but CD4+ T cells express many cytokines thought to Adenosine triphosphate play a role in the regulation of one or both of these processes [71–74]. In particular the pleiotropic protein, thrombospondin-1 (TSP-1), was identified as a critical mediator of CD4+ T cell-mediated

sustained tumour regression upon MYC inactivation. TSP-1 could potentially play a multi-faceted role in contributing to remodelling of the tumour microenvironment upon oncogene inactivation. Produced by a panoply of cells, including activated CD4+ T cells [69,75], TSP-1 is a potent anti-angiogenic and immune modulatory cytokine that can induce apoptosis of endothelial cells and regulate T cell chemotaxis [76]. Moreover, TSP-1 has been shown to activate latent transforming growth factor (TGF)-β[77]. Notably, TGF-β can play a tumour suppressive role in the tumour microenvironment [78,79]. Also, TGF-β can contribute to both the restraint of tumour onset as well as oncogene addiction through the regulation of cellular senescence upon MYC activation and inactivation [42,80]. Thus, it is tempting to speculate that TSP-1 may contribute to oncogene addiction via an influence on TGF-β.

Interestingly, Ehirchiou et al. [44] found that TH17 cells in lymph nodes may negatively interfere with tolerance induction to fed allergens, which suggests that IL-17A could be involved in the allergic airway sensitization

in our i.n. model. Apparently, the youngest mice had augmented airway responses compared with older mice. In both the i.p. (10 μg) Adriamycin in vitro and i.n. model, the youngest mice had higher BALF eosinophil influx and higher cytokine secretion than older mice. In the i.n. model, the OVA-only immunized 1-week-old mice also presented with increased OVA-specific IgG1 levels accompanied by a neutrophil inflammation in BALF. It may be argued that endotoxin contamination of the OVA could have an inflammatory effect particularly in the youngest mice. However, acute lung responses to endotoxin did not differ between newborn and adult mice [45], which argue against endotoxin as an explanation for the observed age differences. Allergen doses that

induce tolerance in adult rodents may, when applied mucosally in newborns, induce IgE sensitization [46, 47]. However, we did not observe effects on OVA-specific IgE after i.n. exposure to OVA alone. If the inflammation in mice sensitized at 1 week of age may be ascribed to an IgG-immune-complex-induced reaction cannot be defined from this study, but would explain the neutrophil-dominated Crizotinib chemical structure inflammation [48, 49]. Whether the general propensity to elevated inflammation in very young mice may be

see more linked to early onset of allergy and asthma in children remains to be determined. Further, half of children with early-onset asthma outgrow their disease [50]. It could be speculated that this is because of the maturation of the immune system, because bronchial hyperreactivity and airway inflammation persisted for a shorter time in mice sensitized when newborn compared to when sensitized as 8 weeks old [34]. Although ‘new’ allergy can occur throughout life, generally, allergy prevalence and severity tend to decrease after young adult life [51], and TH2-type responses may weaken with age [52]. Immunological ageing studies have included mice of much higher age than the present study. However, our study clearly demonstrates that age may exert a pronounced effect on experimental allergy even in mice up to 5–6 months of age. Further, allergy responses in female and male mice may be affected differently by age and allergen doses. The study also indicates that to develop appropriate models of allergy in children, adults and aged humans, good knowledge of age-related effects in human allergic diseases is required. The data presented here demonstrated that age, sex and immunization dose interact to be significant determinants of experimental allergy. Therefore, optimal modelling must be performed to mimic human disease. The study was financed by The Norwegian Research Council.