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Background Regulatory T cells (Tregs) are key players in controlling the development of airway inflammation. However, their role in the mechanisms leading to tolerance in established allergic asthma is unclear. Objective To examine the role of Tregs in tolerance induction in a murine model of asthma. Methods Ovalbumin (OVA) sensitized asthmatic mice were depleted or not of CD25+ T cells by anti-CD25 PC61 monoclonal antibody (mAb) before intranasal treatment (INT) with OVA, then challenged with OVA aerosol. To further evaluate the respective regulatory activity of CD4+CD25+ and CD4+CD25− T cells, both T cell subsets were transferred from tolerized or non-tolerized animals to asthmatic recipients. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. Results Intranasal treatment with OVA led to increased levels of IL-10, TGF-β and IL-17 in lung homogenates, inhibition of eosinophil recruitment into the BALF and antigen specific T cell hyporesponsiveness. CD4+CD25+Foxp3+ T cells were markedly upregulated in lungs and suppressed in vitro and in vivo OVA-specific T cell responses. Depletion of CD25+ cells before OVA INT severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge. However, the transfer of CD4+CD25− T cells not only suppressed antigen specific T cell responsiveness but also significantly reduced eosinophil recruitment as opposed to CD4+CD25+ T cells. As compared with control mice, a significantly higher proportion of CD4+CD25− T cells from OVA treated mice expressed mTGF-β. Conclusion Both CD4+CD25+ and CD4+CD25− T cells appear to be essential to tolerance induction. The relationship between both subsets and the mechanisms of their regulatory activity will have to be further analyzed. [ABSTRACT FROM AUTHOR]

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The article focuses on the Rheumatoid factor (RF) which is an autoantibody and has a specificity to the Fc portion of IgG. It has been demonstrated that IgM RF can be formed spontaneously [1] and following milogenic or antigenic stimulation in non-autoimmune strains of mice [2-4]. Although non-autoimmune mice produce RF which are nearly always restricted to the IgM class, a lupusprone MRL/Mpi-lprltpr (MRL-tpr) strain spontaneously produces IgG RF as well as IgM RF [5]. In fact, the presence of intermediate-sized immune complexes consisting of IgG RF [6,7] similar to those found in sera or synovial fluids (Vom patients with rheumatoid arthritis [8,9], is a unique feature of MRL-lpr mice among several strains oflupus-prone mice.

Background Venom immunotherapy is definitely indicated in severe systemic anaphylactic reactions to bee stings, but is not devoided of risks of anaphylaxis. Safer methods of immunotherapy need to be developed. Objective To delineate phospholipase A2 T-cell epitopes using short 15mer vs long 40-60mer overlapping peptides, and to approach the potential interest of a venom immunotherapy based on the use of long peptides (1-60, 51-99, 90-134) mapping the whole phospholipase A2 molecule vs a restricted number of immunodominant epitopes. Methods Proliferation of a CD8+ T cell depleted peripheral blood mononuclear cell fraction and short-term T-cell lines from unselected bee venom hypersensitive patients in response to phospholipase A2 synthetic peptides. Results Whereas T-cell proliferation of 15mer overlapping peptides was weak, T-cell response to long overlapping peptides was in contrast vigorous in all patients, mostly directed to C-terminal peptide 90-134. Our results did not support the concept of rare dominant T-cell epitopes, and disclosed T-cell responses to multiple epitopes in several patients. No significant IgE-binding to long overlapping peptides was detected except in one patient against peptide 90-134. Conclusion 15mer peptides might not be sensitive enough to fully delineate all potential T-cell epitopes scatter along the allergen. Since they do not bind IgE in vitro or only weakly, and taking into account a T-cell response frequently directed to multiple epitopes, long overlapping peptides may represent ideal tools for immunotherapy. [ABSTRACT FROM AUTHOR]

Background Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down-regulate the IgE response. Objective To monitor the long-term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis. Methods CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2 ) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase. Results Low-dose immunization with PLA2 (0.1 µg) favoured a long-term, specific T helper (Th)2 response with high IgE and IL-4 production in contrast to high-dose PLA2 (10 µg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL-4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2 , which was also dose-dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen-specific, it could be induced in the high- and low-dose immunization groups, and was not solely dependent on IgE levels. Conclusion Though low-dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model-based data. [ABSTRACT FROM AUTHOR]