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Subversion of T regulatory cells in atopic dermatitis by superantigens
The Editors’ Choice Donald Y.M. Leung, MD, PhD Harold S. Nelson, MD Stanley J. Szefler, MD William W. Busse, MD
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 113
NUMBER 4
A primary prevention trial in childhood asthma Because the increase in asthma in developed countries is likely to be due to changing environmental exposures, identification and reduction of these exposures should reverse the trend toward increasing asthma. This proposition is being prospectively studied in the Canadian Asthma Primary Prevention Study. In this issue of the Journal, Becker and coworkers (p 650) report the 2-year followup results of this study. A cohort of children was identified on the basis of an immediate family history of asthma or allergy. The subjects were then randomized into intervention and control groups. The intervention included (a) house dust control measures, (b) recommendations for avoidance of pets, environmental tobacco smoke, and day care during the first year, and (c) only breastfeeding or use of partially hydrolyzed whey formula until at least the age of 4 months. The investigators had previously reported that asthma was significantly reduced by 34% at 1 year of age. At 2 years of age, 476 children remained in the study. Significantly fewer children had asthma in the intervention group than in the control group (16.3% vs 23.0%), and 60% fewer of the intervention group
Do inhaled corticosteroids suppress the immune response to influenza vaccine in patients with asthma? Annual influenza vaccination is recommended for all asthmatic patients to decrease the morbidity associated with influenza virus infection. Asthmatic patients are often treated with inhaled corticosteroids (ICSs). High-dose ICS therapy can be associated with systemic adverse effects. In this issue of the Journal, Hanania and colleagues (p 717) conducted a study to determine whether maintenance therapy with ICS in asthmatic patients affects the immune response to influenza vaccine. A total of 294 subjects
Subversion of T regulatory cells in atopic dermatitis by superantigens Atopic dermatitis (AD) is often triggered by superantigenproducing Staphylococcus aureus. Recent studies have demonstrated that CD4+CD25+ T regulatory (Treg) cells play an important role in controlling airway inflammation in animal models of asthma. Patients with XLAAD/IPEX disease specifically lack CD4+CD25+ Treg cells and develop severe eczema and elevated IgE levels. However, it is not known whether CD4+CD25+ Treg cells also play an important role in human allergic diseases such as AD. These studies prompted Ou et al, in this month’s issue of the Journal (p 756), to ask whether patients with AD have low numbers
J ALLERGY CLIN IMMUNOL
Incidence of asthma in high-risk infants.
children had persistent asthma (4.9% vs 11.3%). There was no significant difference for atopy between the intervention and control groups, but day care attendance any time during the first 12 months reduced atopy at 2 years (5% vs 15.7%). The authors conclude that this multifaceted intervention program in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.
received either placebo or inactivated trivalent influenza vaccine. Study subjects were categorized according to their use of ICSs (group 1, medium-dose or high-dose ICS; group 2, no or low-dose ICS). Serum hemagglutination inhibition antibody levels to the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine. The investigators observed similar levels of immune response in the 2 groups. However, subgroup analyses demonstrated an attenuated response to the influenza B virus antigen in patients receiving high-dose ICSs compared with those not taking ICSs. The authors conclude that though the immune response to the A antigens of the inactivated influenza vaccine in asthmatic subjects is not adversely affected by ICS therapy, use of high-dose ICSs might lead to a diminished response to the influenza B antigen.
of CD4+CD25+ Treg cells or a deficient function of Treg cells. Surprisingly, CD4+CD25+ T cells were significantly elevated in patients with AD in comparison with asthmatic individuals or nonatopic normal control subjects. In consistency with known properties of Treg cells, CD4+CD25+ cells were anergic to anti-CD3 stimulation. When CD4+CD25+ cells from each study group were mixed with CD4+CD25ÿ cells, proliferative responses were equally suppressed after anti-CD3 stimulation. However, after staphylococcal enterotoxin B stimulation, CD4+CD25+ cells were no longer anergic. Furthermore, when CD4+CD25+ cells were mixed with CD4+CD25ÿ cells and stimulated with staphylococcal enterotoxin B, the suppressive function of Treg cells was reversed. These data suggest a novel mechanism by which superantigens could augment T-cell activation in AD.
April 2004 Page 583
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 113
NUMBER 4
A primary prevention trial in childhood asthma Because the increase in asthma in developed countries is likely to be due to changing environmental exposures, identification and reduction of these exposures should reverse the trend toward increasing asthma. This proposition is being prospectively studied in the Canadian Asthma Primary Prevention Study. In this issue of the Journal, Becker and coworkers (p 650) report the 2-year followup results of this study. A cohort of children was identified on the basis of an immediate family history of asthma or allergy. The subjects were then randomized into intervention and control groups. The intervention included (a) house dust control measures, (b) recommendations for avoidance of pets, environmental tobacco smoke, and day care during the first year, and (c) only breastfeeding or use of partially hydrolyzed whey formula until at least the age of 4 months. The investigators had previously reported that asthma was significantly reduced by 34% at 1 year of age. At 2 years of age, 476 children remained in the study. Significantly fewer children had asthma in the intervention group than in the control group (16.3% vs 23.0%), and 60% fewer of the intervention group
Do inhaled corticosteroids suppress the immune response to influenza vaccine in patients with asthma? Annual influenza vaccination is recommended for all asthmatic patients to decrease the morbidity associated with influenza virus infection. Asthmatic patients are often treated with inhaled corticosteroids (ICSs). High-dose ICS therapy can be associated with systemic adverse effects. In this issue of the Journal, Hanania and colleagues (p 717) conducted a study to determine whether maintenance therapy with ICS in asthmatic patients affects the immune response to influenza vaccine. A total of 294 subjects
Subversion of T regulatory cells in atopic dermatitis by superantigens Atopic dermatitis (AD) is often triggered by superantigenproducing Staphylococcus aureus. Recent studies have demonstrated that CD4+CD25+ T regulatory (Treg) cells play an important role in controlling airway inflammation in animal models of asthma. Patients with XLAAD/IPEX disease specifically lack CD4+CD25+ Treg cells and develop severe eczema and elevated IgE levels. However, it is not known whether CD4+CD25+ Treg cells also play an important role in human allergic diseases such as AD. These studies prompted Ou et al, in this month’s issue of the Journal (p 756), to ask whether patients with AD have low numbers
J ALLERGY CLIN IMMUNOL
Incidence of asthma in high-risk infants.
children had persistent asthma (4.9% vs 11.3%). There was no significant difference for atopy between the intervention and control groups, but day care attendance any time during the first 12 months reduced atopy at 2 years (5% vs 15.7%). The authors conclude that this multifaceted intervention program in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.
received either placebo or inactivated trivalent influenza vaccine. Study subjects were categorized according to their use of ICSs (group 1, medium-dose or high-dose ICS; group 2, no or low-dose ICS). Serum hemagglutination inhibition antibody levels to the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine. The investigators observed similar levels of immune response in the 2 groups. However, subgroup analyses demonstrated an attenuated response to the influenza B virus antigen in patients receiving high-dose ICSs compared with those not taking ICSs. The authors conclude that though the immune response to the A antigens of the inactivated influenza vaccine in asthmatic subjects is not adversely affected by ICS therapy, use of high-dose ICSs might lead to a diminished response to the influenza B antigen.
of CD4+CD25+ Treg cells or a deficient function of Treg cells. Surprisingly, CD4+CD25+ T cells were significantly elevated in patients with AD in comparison with asthmatic individuals or nonatopic normal control subjects. In consistency with known properties of Treg cells, CD4+CD25+ cells were anergic to anti-CD3 stimulation. When CD4+CD25+ cells from each study group were mixed with CD4+CD25ÿ cells, proliferative responses were equally suppressed after anti-CD3 stimulation. However, after staphylococcal enterotoxin B stimulation, CD4+CD25+ cells were no longer anergic. Furthermore, when CD4+CD25+ cells were mixed with CD4+CD25ÿ cells and stimulated with staphylococcal enterotoxin B, the suppressive function of Treg cells was reversed. These data suggest a novel mechanism by which superantigens could augment T-cell activation in AD.
April 2004 Page 583