Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children

Abstract

Background Childhood represents an immunological window of vulnerability in which individuals are at increased risk for both serious infections and development of allergic diseases, particularly affecting the airways. However, little is known about how the airway mucosal immune system is organised and functions during early age. Here, the organisation of immune cells in bronchial mucosa of children was characterised.Methods Immunophenotyping was performed on mucosal samples obtained postmortem from nine children aged 2e15 years without any history of atopic manifestations or any signs of respiratory disease, who died from non-inflammatory causes.Results In all nine cases, isolated lymphoid follicles (ILFs), interpreted as bronchus-associated lymphoid tissue (BALT), were found, constituting an average frequency of 60 ILFs/cm 2 of airway mucosal surface. Outside these ILFs, dense networks of CD11c + myeloid dendritic cells (DCs), CD68 + macrophages and CD3 + CD45RAÀ memory T cells were found. Plasmacytoid DCs occurred in low numbers. Importantly, intraepithelial antigen-presenting cells were found to extend cellular projections into the airway lumen. Conclusion The density and location of antigenpresenting cells and T cells in this age group are similar to those observed in adults. However, in contrast to adults, BALT appears to be a normal feature of the airway mucosa throughout childhood, suggesting that these structures contribute to regional immunity and homeostasis. This indicates that the local immune system in the airways of children has unique features which should be taken into account, not only when studying airway immunology and immunopathology, but also in the development of mucosal vaccines.

The Mucosal B Cell System

“…In contrast to tonsils, however, the anlage of which appears at the same fetal age as that of PPs (von Gaudecker and Müller-Hermelink, 1982), the organogenesis of murine NALT begins after birth, like murine ILFs (Kunisawa et al, 2008). Like murine BALT (Moyron-Quiroz et al, 2004), human BALT and nasal ILFs also seem to be inducible because these structures show large individual variability in their appearance (Tschering and Pabst, 2000;Debertin et al, 2003;Heier et al, 2008Heier et al, , 2011.…”

“…However, induction of mucosal immunity can take place also in nasopharynxassociated lymphoid tissue (NALT), including the unpaired nasopharyngeal tonsil (adenoids) and the paired palatine tonsils (see Chapter 103), as well as other lymphoepithelial structures of Waldeyer's pharyngeal ring (Brandtzaeg, 1987(Brandtzaeg, , 2011aBrandtzaeg and Johansen, 2005). BALT may also contribute, but this type of MALT is normally absent or rare in healthy lungs of adults although often present in children and adolescents-regularly being detected shortly after birth (Hiller et al, 1998;Heier et al, 2008Heier et al, , 2011.…”

“…These organs make up most of Waldeyer's pharyngeal lymphoid ring and may play a major role in mucosal immunity in human airways, because BALT structures are not present or are quite rare in normal lungs of adults and are seen in only 40-50% of ordinary bronchial specimens from adolescents and children (Hiller et al, 1998), although they are regularly present at low frequency shortly after birth (Heier et al, 2008(Heier et al, , 2011. Also, human nasal mucosa contains only occasional ILFs and they are undetectable in mucosal specimens from at least 60% of children below 2 years of age (Debertin et al, 2003).…”

Immunobiology of the Tonsils and Adenoids

“…Although ILFs do not regularly exist in the normal adult lung (Pabst and Tschernig, 2010), such BALT structures were found in all of nine large bronchial autopsy specimens of children aged 2-15 years who died from traumatic causes and had no airway disease (Heier et al, 2011). Likewise, in large autopsy specimens of nasal mucosa occasional scattered ILFs were seen in 38% of children below 2 years of age (Debertin et al, 2003).…”

B-lymphocyte lineage cells and the respiratory system

“…162 Other lymphoid aggregates are also found in the human larynx epithelium (termed laryngeal associate lymphoid tissue LALT) and have been shown to persist into adulthood. 163 In the lower airway, bronchial-associated lymphoid tissue (BALT) is found rarely in the lungs of human fetuses without the presence of intrauterine infection 164,165 or healthy adults without a history of pulmonary disease. 166,167 This situation is unlike that in rats where BALT is found in germ-free pups as early as four days after birth along bifurcations of the upper bronchi.…”