Development of Bronchus-Associated Lymphoid Tissue in Chronic Hypersensitivity Pneumonitis

doi:10.1378/chest.115.2.357

Chest

Volume 115, Issue 2, February 1999, Pages 357-363

https://doi.org/10.1378/chest.115.2.357 Get rights and content

Study objectives

Bronchus-associated lymphoid tissue (BALT) is well defined in animals. In humans, however, BALT has been reported to be inducible under pathologic conditions, such as chronic respiratory infection, although it is not present in healthy adults. Thus, induced BALT is considered to be involved in the mucosal immunity of the human lung under these conditions. However, there have been few studies to investigate BALT development in hypersensitivity pneumonitis. The aim of this study was to examine the presence of BALT in hypersensitivity pneumonitis, especially in its chronic form.

Methods

The subjects included five patients with chronic hypersensitivity pneumonitis (CHP) diagnosed from clinical and histologic findings. We investigated histologically the development of BALT in these patients. Further, the cellular distribution of BALT was also examined by immunohistochemistry.

Results

BALT was present in three of five patients with CHP. Immunohistochemical examination revealed the follicular area of BALT to be composed mainly of B cells, while the parafollicular area comprised predominantly T cells. Centroblasts located in the germinal center of BALT expressed Ki-67 antigen, a marker of cell proliferation, suggesting that these cells were actively proliferating after antigenic stimulation. Cells expressing bcl-2, which is present primarily on memory B cells, were confined to the follicular area, devoid of any germinal centers. S-100-positive, CD1a-negative interdigitating dendritic cells were observed in the dome area of BALT.

Conclusions

These observations suggest that chronic antigenic stimulation and/or inflammation in CHP may cause BALT development, which, in turn, is likely to play an important role in the mucosal immune response of this disease.

Section snippets

Patients

The study population consisted of five patients with CHP who underwent an open lung biopsy. The diagnosis was made from a compatible exposure history to an antigen or environmental factor, the presence of long-standing clinical and radiologic findings, and a lung biopsy showing characteristic histologic features. There were two men and three women, with a mean age of 50 years. One subject was a current smoker at the time of diagnosis; the other four were nonsmokers. All had chronic dyspnea and

Clinical Features

Clinical characteristics of five patients with CHP are summarized in Table 1. All cases, except for case 2, had hypoxemia. Pulmonary function tests showed restrictive impairment in all cases. In the BAL fluid, an increase in the percentage of lymphocytes was observed in every case except case 3. However, the CD4 to CD8 ratio of lymphocytes in their BAL fluid varied. Cases 1 and 3 through 5 developed symptoms associated with the greenhouse and home, respectively, and their environmental

Discussion

BALT has been reported to play a crucial role in the development of a local immune response to inhaled antigens in animals, such as rabbits and rats.¹^,2 However, there are significant differences between species in the degree of organization of BALT. In human lungs, no organized BALT is found under normal circumstances.⁶ Thus, in contrast to GALT, most of the studies on BALT have been performed in animals. A few reports focused on BALT in humans.⁷^,8^,16^,17 We previously reported the development

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Pulmonary follicular lymphoid hyperplasia in a child with HTLV-III-related immunodeficiency
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Anatomical uniqueness of the mucosal immune system (GALT, NALT, iBALT) for the induction and regulation of mucosal immunity and tolerance
2019, Mucosal Vaccines: Innovation for Preventing Infectious Diseases
Mucosal surfaces lining the lung and the gut are constantly exposed to environmental antigens, commensal organisms, and pathogens. Consequently, the host’s immune system devotes enormous resources to the defense of these tissues. Although mucosal immune responses must be sufficiently strong to eliminate pathogens, they must also have mechanisms to prevent excessive inflammation and initiate epithelial repair. Importantly, mucosal immune responses are initiated and regulated by a variety of mucosal lymphoid tissues, collectively known as mucosa-associated lymphoid tissue (MALT). This chapter describes the unique developmental, architectural, and functional features of the MALT and how those features facilitate the local immune response at each site.
Structure, Organization, and Development of the Mucosal Immune System of the Respiratory Tract
2015, Mucosal Immunology: Fourth Edition
The respiratory tract is served by a variety of lymphoid tissues, including the tonsils, adenoids, nasal-associated lymphoid tissue (NALT), and bronchus-associated lymphoid tissue (BALT), as well as the lymph nodes that drain the upper and lower respiratory tract. Each of these tissues uses unique mechanisms to acquire antigens and respond to pathogens in the local environment and supports immune responses that are tailored to protect those locations. This chapter will review the important features of NALT and BALT and define how these tissues contribute to immunity in the upper and lower respiratory tract, respectively.
The development and function of mucosal lymphoid tissues: A balancing act with micro-organisms
2014, Mucosal Immunology
Mucosal surfaces are constantly exposed to environmental antigens, colonized by commensal organisms and used by pathogens as points of entry. As a result, the immune system has devoted the bulk of its resources to mucosal sites to maintain symbiosis with commensal organisms, prevent pathogen entry, and avoid unnecessary inflammatory responses to innocuous antigens. These functions are facilitated by a variety of mucosal lymphoid organs that develop during embryogenesis in the absence of microbial stimulation as well as ectopic lymphoid tissues that develop in adults following microbial exposure or inflammation. Each of these lymphoid organs samples antigens from different mucosal sites and contributes to immune homeostasis, commensal containment, and immunity to pathogens. Here we discuss the mechanisms, mostly based on mouse studies, that control the development of mucosal lymphoid organs and how the various lymphoid tissues cooperate to maintain the integrity of the mucosal barrier.
B-lymphocyte lineage cells and the respiratory system
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Adaptive humoral immune responses in the airways are mediated by B cells and plasma cells that express highly evolved and specific receptors and produce immunoglobulins of most isotypes. In some cases, such as autoimmune diseases or inflammatory diseases caused by excessive exposure to foreign antigens, these same immune cells can cause disease by virtue of overly vigorous responses. This review discusses the generation, differentiation, signaling, activation, and recruitment pathways of B cells and plasma cells, with special emphasis on unique characteristics of subsets of these cells functioning within the respiratory system. The primary sensitization events that generate B cells responsible for effector responses throughout the airways usually occur in the upper airways, tonsils, and adenoid structures that make up the Waldeyer ring. On secondary exposure to antigen in the airways, antigen-processing dendritic cells migrate into secondary lymphoid organs, such as lymph nodes, that drain the upper and lower airways, and further B-cell expansion takes place at those sites. Antigen exposure in the upper or lower airways can also drive expansion of B-lineage cells in the airway mucosal tissue and lead to the formation of inducible lymphoid follicles or aggregates that can mediate local immunity or disease.
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2013, Thorax
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To explore the hypothesis that interfaces between the alveolar lumen and lymphoid aggregates (LAs) provide a structural basis for increased alveolar antigen uptake in COPD lungs.
Lung samples from patients with mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), moderate–severe (GOLD II–III), and very severe (GOLD IV) COPD were subjected to detailed histological assessments of adaptive immune system components. Never smokers and smokers without COPD served as controls.
Quantitative histology, involving computerised three-dimensional reconstructions, confirmed a rich occurrence of alveolar-restricted LAs and revealed, for the first time, that the vast majority of vascular or bronchiolar associated LAs had alveolar interfaces but also an intricate network of lymphatic vessels. Uniquely to COPD lungs, the interface epithelium had transformed into a columnar phenotype. Accumulation of langerin (CD207)⁺ dendritic cells occurred in the interface epithelium in patients with COPD but not controls. The antigen-capturing capacity of langerin+ dendritic cells was confirmed by increased alveolar protrusions and physical T cell contact. Several of these immune remodelling parameters correlated with lung function parameters.
Severe stages of COPD are associated with an emergence of remodelled and dendritic cell-rich alveolar–lymphoid interfaces. This novel type of immune remodelling, which predicts an increased capacity to respond to alveolar antigens, is suggested to contribute to aggravated inflammation in COPD.
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Chest

Study objectives

Methods

Results

Conclusions

Section snippets

Patients

Clinical Features

Discussion

References (22)

Bronchus-associated lymphoid tissue in human lung: correlation of hyperplasia with chronic pulmonary disease

Clin Immunol Immunopathol

Environmental mycological studies on the causative agent of summer-type hypersensitivity pneumonitis

J Allergy Clin Immunol

Serotype-related antigen of Trichosporon cutaneum in the induction of summer-type hypersensitivity pneumonitis: correlation between serotype of inhalation challenge-positive antigen and that of the isolates from patients' homes

J Allergy Clin Immunol

Bronchial lymphoid tissue: I. Morphologic characteristics

Lab Invest

Bronchial lymphoid tissue: II. Functional characteristics

Lab Invest

Gut and bronchus associated lymphoid tissue: an overview

Adv Exp Med Biol

Functional architecture of bronchial lymphoid tissue and lymphoepithelium in pulmonary cell-mediated reactions in the rabbit

J Reticuloendothel Soc

Induction of antigen-specific IgA-forming cells in the upper respiratory mucosa

Ann Otol Rhinol Laryngol

Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans?

Am J Respir Cell Mol Biol

Pulmonary follicular lymphoid hyperplasia in a child with HTLV-III-related immunodeficiency

Pediatr Pulmonol

Study of bronchus-associated lymphoid tissue in patients with diffuse panbronchiolitis

Am Rev Respir Dis

Cited by (83)

Anatomical uniqueness of the mucosal immune system (GALT, NALT, iBALT) for the induction and regulation of mucosal immunity and tolerance

Structure, Organization, and Development of the Mucosal Immune System of the Respiratory Tract

The development and function of mucosal lymphoid tissues: A balancing act with micro-organisms

B-lymphocyte lineage cells and the respiratory system

Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease

Occupational extrinsic allergic alveolitis

Chest

Clinical InvestigationsHYPERSENSITIVITYDevelopment of Bronchus-Associated Lymphoid Tissue in Chronic Hypersensitivity Pneumonitis

Study objectives

Methods

Results

Conclusions

Section snippets

Patients

Clinical Features

Discussion

Clin Immunol Immunopathol

J Allergy Clin Immunol

J Allergy Clin Immunol

Bronchial lymphoid tissue: I. Morphologic characteristics

Lab Invest

Bronchial lymphoid tissue: II. Functional characteristics

Lab Invest

Gut and bronchus associated lymphoid tissue: an overview

Adv Exp Med Biol

Functional architecture of bronchial lymphoid tissue and lymphoepithelium in pulmonary cell-mediated reactions in the rabbit

J Reticuloendothel Soc

Induction of antigen-specific IgA-forming cells in the upper respiratory mucosa

Ann Otol Rhinol Laryngol

Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans?

Am J Respir Cell Mol Biol

Pulmonary follicular lymphoid hyperplasia in a child with HTLV-III-related immunodeficiency

Pediatr Pulmonol

Study of bronchus-associated lymphoid tissue in patients with diffuse panbronchiolitis

Am Rev Respir Dis

Clinical Investigations
HYPERSENSITIVITY
Development of Bronchus-Associated Lymphoid Tissue in Chronic Hypersensitivity Pneumonitis