Allergic airway inflammation is exacerbated during acute influenza infection and correlates with increased allergen presentation and recruitment of allergen-specific T-helper type 2 cells.

BACKGROUND: Respiratory viral infections are a leading cause of the hospitalization of asthmatics, however, the cellular immunological interactions which underlie these two diseases remain elusive. OBJECTIVE: We sought to characterize the effect influenza viral infection has on allergic airway inflammation and to identify the cellular pathways involved. METHODS: We have used an ovalbumin (OVA) model of allergic airway inflammation, which involves sensitization of animals with OVA adsorbed in alum adjuvant followed by an intranasal challenge with OVA in phosphate-buffered saline. To study T cell recruitment into the lung, we adoptively transferred in vitro activated T cell receptor-transgenic T cells, which were subsequently identified by fluorescence-activated cell sorting (FACS) analysis. In addition, to study in vivo dendritic cell (DC) migration, we administered fluorescently labelled dextran and identified DCs that had phagocytosed it by FACS analysis. RESULTS: We found that different stages of influenza infection had contrasting effects upon the outcome of OVA-induced allergic airway inflammation. The allergic response against OVA was exacerbated during the acute stage of influenza infection; however, mice were protected against the development of airway eosinophilia at late time-points following infection. We investigated the mechanisms responsible for the virus-induced exacerbation and found that the response was partially independent of IL-4 and that there was increased delivery of inhaled allergens to the draining lymph node during the acute stage of the infection. In addition, virus-induced inflammation in the lung and draining lymph node resulted in the non-specific recruitment of circulating allergen-specific effector/memory cells. CONCLUSION: In addition to virus-mediated damage to the lung and airways, influenza viral infection can also enhance unrelated local allergic responses.

Dendritic cell elimination as an assay of cytotoxic T lymphocyte activity in vivo.

We show in this paper that the survival of antigen-loaded dendritic cells in vivo may be used as a sensitive readout of CTL activity. We have previously shown that dendritic cells labeled with the fluorescent dye CFSE and injected sub-cutaneously into mice migrate spontaneously to the draining lymph node where they persist for several days. In the presence of effector CTL responses, dendritic cells loaded with specific antigen rapidly disappear from the draining lymph node. In this paper we extend the above observations and set up a simple and sensitive method to reveal CTL activity in individual mice in vivo. Dendritic cells were labeled with two different fluorochromes, loaded with antigen or left untreated, and mixed together before injection into mice. We show that only the dendritic cells loaded with specific antigen were cleared from the draining lymph node, while dendritic cells not loaded with antigen remained unaffected. Cytotoxic responses generated by immunization with peptide-loaded dendritic cells, or by infection with influenza virus, could be revealed using this method. Comparison of the differential survival of dendritic cells populations mixed together also allowed us to accurately evaluate the disappearance of dendritic cells, irrespective of variability in the injection site and other parameters. Given the ability of dendritic cells to efficiently take up and present complex antigens, nucleic acids and apoptotic bodies, this method may also allow the evaluation of cytotoxic activity against antigens that are not characterized in terms of peptide epitopes.

Development of an asthma vaccine: research into BCG.

Asthma is an atopic disorder characterised by the activation and recruitment of eosinophils to the lung resulting in chronic swelling and inflammation of the airways. Allergic disorders such as atopic asthma and dermatitis have been increasingly prevalent in developed countries, and the inverse correlation between exposure to major diseases such as tuberculosis and atopy prevalence has been reported. Intranasal administration of Mycobacterium bovis-Bacillus Calmette-Guerin (BCG) has been demonstrated to suppress airway eosinophilia in a model of atopic asthma. This immunomodulation is attributed to the ability of interferon (IFN)-gamma produced by BCG-specific T(H)1 lymphocytes to inhibit the development of lung T(H)2 responses such as airway eosinophilia. The mechanism of IFNgamma-induced inhibition is yet to be defined, but could involve activation of macrophages, direct suppression of developing T(H)2 lymphocytes, or altered dendritic cell activation and antigen presentation. Mycobacteria such as BCG and certain mycobacterial fractions are strong inducers of a T(H)1 immune response. The effectiveness of BCG in inhibiting atopic airway eosinophilia suggests its potential as a useful therapeutic agent in the treatment of atopic asthma.

Effects of weight loss and exercise training on natural killer cell activity in obese women.

PURPOSE: The purposes of this study were two-fold: (1) to evaluate the effects of an 8-wk weight loss program on natural killer (NK) cell activity in obese women and 2) to determine whether an additional program of combined aerobic and resistance exercise training modified the effects of caloric restriction on immune function. METHODS: Twenty-two healthy obese women with a mean weight of 96.9 +/- 14 kg and age of 38 +/- 7 yr were randomly assigned to diet-alone (D) or diet-plus-exercise training (D + EX) conditions. Subjects consumed 950 kcal.d-1 using prepackaged portion-controlled foods. Subjects in the D + EX group participated 3 times.wk-1 in a supervised program of light-to moderate-intensity aerobic activity and resistance training. Data were analyzed using a repeated measures ANOVA. RESULTS: After 8 wk of treatment, body weight decreased significantly in both groups (10.8% in D vs 11.4% in D + EX), whereas absolute and relative VO2peak increased in only D + EX (12.3% in D vs 57.7% in D + EX). Both groups experienced significant decreases in peripheral blood leukocytes and lymphocytes, although cell numbers remained within clinically normal range at week 8. NK cell (CD56+) proportion was unchanged in both groups after weight loss. The proportion of peripheral mononuclear cells expressing the interleukin-2 receptor-alpha (IL-2R alpha) (CD25+) decreased significantly (25.2%) in D and was unchanged in D + EX, resulting in a significant difference between groups at week 8. NK cell cytotoxicity was suppressed in D and unchanged in D + EX after treatment. Changes in NK cell activity were significantly correlated with proportional changes in (CD25+) (r = 0.584, P = 0.022), but not CD56+. CONCLUSIONS: A combined program of light- to moderate-intensity aerobic and resistance exercise offsets the apparent decrement in NK cell activity associated with weight loss.