Maturation of immune responses at the beginning of asthma,☆☆

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Abstract

The prevalence of childhood asthma appears to be increasing worldwide. A critical element in the development of childhood asthma is maturation of the child’s immune system. Most asthmatic children have a history of recurrent lower respiratory tract illnesses associated with airway obstruction during the first year of life. Most infants and young children who will go on to have persistent wheezing and asthma show high IgE production and eosinophilic immune responses at the time of their first viral lower respiratory tract illness. 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 prevention of asthma. (J Allergy Clin Immunol 1999;103:355-61.)

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

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    Reprint requests: Fernando D. Martinez, MD, The University of Arizona, PO Box 245030, Tucson, AZ 85724-5030.

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