Bronchial response pattern of antigen presenting cells and regulatory T cells in children below two years of age

Ingvild Heier ¹, Kristiina Malmström ², Anna S Pelkonen ², S. Pekka Malmberg ², Merja Kajosaari ³, Markku Turpeinen ², Harry Lindahl ³, Per Brandtzaeg ¹, Frode L Jahnsen ^4* and Mika J Mäkelä ²

¹ LIIPAT, the Pathology Clinic, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, N-, Norway
² Division of Allergy, Department of Medicine Helsinki University Central Hospital, Helsinki, Finland
³ Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
⁴ LIIPAT, the Pathology Clinic, University of Osl, Norway

^* To whom correspondence should be addressed. E-mail: f.l.jahnsen{at}medisin.uio.no.

Accepted 16 January 2008

Abstract

Background: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen-presenting cells (APC) and regulatory T cells (Tregs) are important modifiers of T-cell immunity, but little is known about their distribution in bronchial mucosa at this age. Here, we examined immunohistochemically the subset distribution of APC and the appearance of Foxp3+ Tregs and bronchus-associated lymphoid tissue (BALT) in children below the age of 2 years with chronic asthma-like symptoms of lower airways.

Methods: Immunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants 4-23 months of age under investigation for airway disease.

Results: A well-developed HLA-DR+ network of antigen presenting cells was present in all samples, approximately 50% of the cells being CD68+ macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR+ cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of antigen-presenting cell subsets and clinical parameters, only the number of intraepithelial CD1a+ dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3+ Tregs were located primarily within these isolated lymphoid follicles.

Conclusion: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Tregs suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy.

Keywords: BALT, airway mucosa, antigen presenting cells, infant, regulatory T cells

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