Development of bronchus-associated lymphoid tissue in chronic hypersensitivity pneumonitis

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.