Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

Abstract

Lymphocytes in the bronchoalveolar space are routinely obtained and examined in lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes were found in regional lymph nodes after intrabronchial instillation, indicating that reentry of lymphocytes from the bronchoalveaolar space into the body is possible. In the present study, the route and kinetics of the reentry of bronchoalveolar lymphocytes were investigated in a congenic rat model using immunohistochemistry on cryostat and semithin sections and confocal laser scanning microscopy. As early as 15 min after intratracheal instillation lymphocytes were found to leave the bronchoalveolar space by transmigration through alveolar but not bronchial epithelium and were observed in interstitial alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes appeared in the draining lymph nodes of the lung with an increase after 24 and 48 hr. The kinetic pattern clearly differed in nondraining lymph nodes and other organs. After 6 hr, only single cells were found in nondraining lymph nodes, spleen, and blood with a slight increase after 24 hr, and only occasionally were single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after instillation. In conclusion, T and B lymphocytes can leave the alveolar space by reentry into the lung tissue through alveolar epithelium. They reach regional lymph nodes by means of lymphatic vessels and are then distributed all over the body to rejoin the systemic immune system. Coming into contact with environmental antigens, these lymphocytes could perform an important function in the lung immune system and might be a target for inhalative therapy. Anat Key words: pulmonary immune system; lung; lymphocytes; bronchoalveolar space; migration; bronchial lymph node; ratThe lungs are permanently in contact with the outside world and confronted with a large number of antigens and potentially harmful infectious agents. The lymphocytes of the pulmonary immune system are located in different lung compartments, e.g., the intravascular pool, the interstitial pool and the bronchoalveolar pool. They recognize foreign antigens specifically and activate the effector mechanisms that are required for host defense. These cells and their ability to migrate between the circulation, sites of antigen exposure, and lymphoid tissue are of critical importance for the generation of the immune response (Pabst and Tschernig, 1995). The complex system of lymphocyte recruitment and recirculation in the lung is still incompletely understood.

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

“…The potential importance of adaptive immunological processes in COPD has lately become a focus of considerable attention (2-10, [13][14][15][16][23][24][25][26][27][28][29]. Among other observations, T lymphocytes are the most numerous inflammatory cell within alveolar walls of COPD patients, and the extent of intrapulmonary lymphocyte infiltrations in situ is closely correlated with various morphometric and physiological measures of disease severity (2)(3)(4)(5)(6).…”

“…However, it is also widely appreciated that lymphocytes readily traffic between inflammatory sites (including lungs), regional lymph nodes, and the systemic circulation, where they can be easily sampled (13). The ability to study disease phenomena using specimens procured by minimally invasive means could be a boon for subsequent biological and clinical investigations.…”

A Single Intratracheal Dose of the Growth Factor Fms-Like Tyrosine Kinase Receptor-3 Ligand Induces a Rapid Differential Increase of Dendritic Cells and Lymphocyte Subsets in Lung Tissue and Bronchoalveolar Lavage, Resulting in an Increased Local Antibody Production

“…29), differs between lung compartments in immune reactions (30). It has to be stressed that only in the lung do lymphocytes traverse a body surface, return later to the organ, and migrate finally to the draining, i.e., the bronchial LN (31). Recently, we proposed a concept of a unique compartment in the lung, the perivascular space (32).…”

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

“…Pulmonary lymphocytes isolated from emphysematous lung tissue are frequently activated (Sullivan et al 2005) and capable of secreting mediators that have been implicated in the pathogenesis of COPD (Grumelli et al 2004). T-cells transit between infl ammatory foci in organs and regional lymph nodes, and at least some proportion of these disease-specifi c lymphocytes also traffi c within lymphatic and blood circulations (Lehmann et al 2001). Our studies of peripheral blood T-lymphocytes in patients with COPD have shown peripheral T-cells (particularly CD8 + ) are more frequently activated and have increased productions of various mediators, and many of these T-cell abnormalities are highly correlated with disease severity (Gadgil et al 2006).…”