Maturation of immune responses at the beginning of asthma☆,☆☆
Section snippets
THE INCEPTION OF ASTHMA
There is little doubt that the first manifestations of asthma can occur at any age. However, longitudinal studies have recently suggested that most school-age asthmatic children have a history of recurrent lower respiratory tract illnesses (LRIs) associated with airway obstruction during the first years of life.2 The relation between these LRIs and the subsequent development of asthma remains controversial. Wheezing LRIs in early life occur mostly in concomitance with viral infections,
DETERMINANTS OF ACUTE RESPONSE TO LRI IN EARLY LIFE
What determines the patterns of response to acute viral LRI in early life is not well understood and has also been scantily studied in humans. Recently, Román et al14 studied the nature of immune responses to confirmed RSV infections in children who were hospitalized for these infections before age 15 months. When compared with control subjects, children infected with RSV showed decreases in CD8+ T cells and in activated suppressor/cytotoxic (CD8+/CD25+) T cells. Cultured PBMCs from
SENSITIZATION TO AEROALLERGENS IN EARLY LIFE AND THE DEVELOPMENT OF ASTHMA
Our work6 and that of others10 has clearly shown that infants and young children with RSV-associated LRIs who will go on to have persistent wheezing are much more likely to become sensitized to local aeroallergens than transient wheezers. The factors that predispose children at risk for asthma to have specific IgE against asthma-related allergens are beginning to be elucidated. Recent seminal studies by Prescott et al25 have contributed very important new data to our understanding of these
MATURATION OF THE ANTIGENPRESENTING CELL SYSTEM AND TH1 /TH2 -LIKE RESPONSES
Studies of immune responses to antigens by cord blood mononuclear cells show that under the right experimental conditions, newborn T cells are capable of mounting an adequate TH1 -like response.33 The low capacity of infant T cells to produce IFN-γ is thus not mainly caused by an intrinsic defect of these cells. It is therefore possible that the defect responsible for the sluggish TH1 -like responses in early life may reside in other cells, and a suitable candidate appears to be the
ROLE OF CD14 IN THE MATURATION OF APCs
The interaction between LPS and APCs is primarily mediated by CD14.41 CD14 is a glycoprotein that is present in tissues in 2 forms: a membrane-bound form (mCD14) and a soluble form (sCD14). mCD14 is mainly found in the surface of monocytes and is anchored to the cell membrane by way of glycosyl-phosphatidylinositol.42 sCD14 lacks the glycosyl-phosphatidylinositol anchor and is quite abundant in the blood serum. Both mCD14 and sCD14 appear to have a variety of functions, but relevant to this
CONCLUSIONS
Most infants and young children who will go onto have persistent wheezing and asthma show high IgE production and eosinophilic immune responses (both in the airways and in circulation) at the timeof their first viral LRI. They also have early IgE-mediated responses to local aeroallergens. Understanding the genetic and environmental factors that regulate the maturation of the immune response during early life will greatly enhance the development of strategies for the primary and secondary
References (51)
- et al.
Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma
J Allergy Clin Immunol
(1998) - et al.
Influence of selective T-lymphocyte depletion on the lung pathology of gnotobiotic calves and the distribution of different T-lymphocyte subsets following challenge with bovine respiratory syncytial virus
Res Vet Sci
(1996) - et al.
Increased levels of IL-4 in CD8+ T cells in atopic asthma
J Allergy Clin Immunol
(1997) - et al.
Association of interleukin-2 and interferon-γ production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy
J Allergy Clin Immunol
(1995) - et al.
Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon?
Immunol Today
(1993) Th1-type immunity is incompatible with successful pregnancy
Immunol Today
(1997)- et al.
Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-γ, natural killer, and lymphokine-activated killer activity by IL-12 in cord blood mononuclear cells
Blood
(1996) - et al.
Recent advances in the study of dendritic cells and follicular dendritic cells
Immunol Today
(1995) - et al.
Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Thl phenotype
Blood
(1997) - et al.
Bacterial lipopolysaccharide contamination of commercial collagen preparations may mediate dendritic cell maturation in culture
J Immunol Methods
(1998)
Evidence for the increase in asthma worldwide
Ciba Found Symp
A community-based study of the epidemiology of asthma. Incidence rates, 1964-1983
Am Rev Respir Dis
Risk factors. Development and natural history
The relationship between impaired lung growth and onset of bronchial asthma in early life
Pediatr Pulmonol
The Tucson Children’s Respiratory Study. II. Lower respiratory tract illness in the first year of life
Am J Epidemiol
Asthma and wheezing in the first six years of life
N Engl J Med
Eosinopenia of acute infection: production of eosinopenia by chemotactic factors of acute inflammation
J Clin Invest
Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis
Arch Dis Child
Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls
Pediatrics
Enhanced arachidonic acid metabolism in alveolar macrophages from wheezy infants. Modulation by dexamethasone
Am J Respir Crit Care Med
Increased spontaneous release of tumour necrosis factor-α by alveolar macrophages from wheezy infants
Eur Respir J
Bronchoalveolar lavage findings suggest two different forms of childhood asthma
Clin Exp Allergy
Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response
Am J Respir Crit Care Med
Immunity and immunopathology to respiratory syncytial virus. The mouse model
Am J Respir Crit Care Med
Phenotypic and functional characterization of T cell lines specific for individual respiratory syncytial virus proteins
J Immunol
Cited by (0)
- ☆
Reprint requests: Fernando D. Martinez, MD, The University of Arizona, PO Box 245030, Tucson, AZ 85724-5030.
- ☆☆
0091-6749/99 $8.00 + 0 1/1/96615