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Background In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4+ effector cells at the airway mucosa orchestrate, and CD4+CD25+ regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues. Objective To determine whether UV-induced changes in CD11c+ cells, CD4+CD25+ effector cells or CD4+CD25+ regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. Methods The phenotype and function of CD11c+ cells and CD4+CD25+ cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA. Results No changes in the function of CD11c+ cells from UV-irradiated mice were observed. CD4+CD25+ cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4+ cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-β mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4+CD25+ cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10. Conclusion Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4+CD25+ cells in the trachea and ADLNs, and not due to UV-induced regulatory cells. Cite this as: J. P. McGlade, D. H. Strickland, M. J. M. Lambert, S. Gorman, J. A. Thomas, M. A. Judge, J. T. Burchell, G. R. Zosky and P. H. Hart, Clinical & Experimental Allergy, 2010 (40) 772–785. [ABSTRACT FROM AUTHOR]

In this article, the extraction of features from acoustic signals generated by a 60-kW direct current electric arc furnace and the use of these features to infer the arc length of the plasma jets in the furnace were considered. A sensor capable of such measurements would be more robust to the unobservable fluctuations of the arc length and would, in principle, allow better control of smelting operations. The collected data comprised sets of five separate 10-second recordings of the acoustic signal, furnace current, and voltage, each at nominal arc lengths of 5, 15, and 25 mm. In the approach, time-frequency features initially were obtained through filter bank analysis of the signals. Reduction of the dimensionality of these filter bank features was then performed using a nonlinear subspace method called kernel Fisher discriminant analysis. Finally, kernel discriminant features were used to infer the arc length via a nearest neighbor classification model that associated three classes of arc lengths (5, 15, and 25 mm) with their corresponding features. The results of the small number of experiments suggest that a significant statistical relationship exists between the length of a plasma arc and its acoustic signal despite potentially large variations in arc phenomena inside the furnace. [ABSTRACT FROM AUTHOR]

Changes in the composition of glycans added to glycoproteins and glycolipids are characteristic of the change to malignancy. Sialyl-Tn (STn) is expressed by 25-30% of breast carcinomas but its expression on normal tissue is highly restricted. Sialyl-Tn is an O-linked disaccharide that can be carried on various glycoproteins. One such glycoprotein MUC1 is expressed by the vast majority of breast carcinomas. Both STn and MUC1 have been considered as targets for immunotherapy of breast cancer patients. Here we used different immunogens to target STn in an MUC1 transgenic mouse model of tumour challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number of targets expressed by the tumour cells, a humoral response can be effective in controlling tumour growth. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) 'pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50,000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-gamma and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. [ABSTRACT FROM AUTHOR]