Bronchus-associated lymphoid tissue (BALT) was first described in the lungs of rabbits and differs greatly between species. It is part of the integrated mucosal immune system. This review clarifies its morphological definition and focuses on the situation in humans. The frequency of BALT at different ages, after chronic stimulation and in different diseases is described. In healthy humans, BALT can only be found in the lungs of children and adolescents. The role of BALT in lung transplantation and in the development of low-grade malignant lymphomas in the airways is also discussed. Furthermore, questions concerning the inducibility of BALT as an entry site for vaccines, and the regulation of its activity for future therapeutic interventions in pulmonary immune reactions are addressed.

Adolescent↗

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Animal models for asthma: controversial aspects and unsolved problems.

The incidence of asthma in children and adults is continuously increasing in the developed countries. Its pathophysiology is still not yet clarified in sufficient detail. Despite a large number of animal models for asthma (mainly rodents), these only partly mimic the situation in humans. Some examples of limitations of using the mouse as an animal model for asthma will be discussed and directions of future research outlined.

Animals↗

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Recruitment of lymphocytes and dendritic cells from the blood to the bronchoalveolar space and the draining lymph nodes after a single intrabronchial application of the lipopeptide MALP-2.

OBJECTIVE: It has been shown previously that the synthetic macrophage-activating lipopeptide, MALP-2, is a potent stimulator of the respiratory immune system and an effective adjuvant in the induction of mucosal immune responses. In this study, the migration route of leukocytes from the blood to the bronchoalveolar space and then to the draining lymph nodes was investigated. METHODS: MALP-2 was intratracheally instilled into lungs of Lewis rats. Bronchoalveolar lavage cells as well as cell preparations of other lung compartments such as the marginal vascular pool, the interstitial pool and also the draining lymph nodes were examined 3 days later. RESULTS: The application of MALP-2 induced a pronounced leukocyte accumulation in the bronchoalveolar space and the lung interstitium but not in the marginal vascular pool. A tendency to increased lymphocyte and dendritic cell numbers was observed in the draining lymph nodes. CONCLUSION: Our data indicate the migration of blood cells into the lung interstitium and the bronchoalveolar space in response to MALP-2. Thus, the immune reaction induced by MALP-2 might be of relevance as an adjuvant treatment in inhalant vaccination strategies in the lung.

Animals↗

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Stimulation of bronchus-associated lymphoid tissue in rats by repeated inhalation of aerosolized lipopeptide MALP-2.

OBJECTIVE: Bronchus-associated lymphoid tissue (BALT) is a part of the integrated mucosal immune system. It may play an important functional role for antigen uptake and induction of specific immune reactions. The aim of this study was to investigate whether it is possible to induce or modulate BALT by the repetitive inhalation of the synthetic lipopeptide MALP-2. METHODS: Female Lewis rats (245 +/- 19 g) inhaled 25 microg of MALP-2 six times at intervals of 1 week. One week after the last inhalation, they were sacrificed. Cells of the bronchoalveolar lavage and the left lung were investigated by flow cytometry. The middle lobe of the right lung was embedded in paraffin. BALT was semiquantitatively measured in 15 serial cross sections per animal. RESULTS: After repetitive inhalation of the diluent as well as MALP-2, BALT was found. The total area was increased after repetitive treatment with MALP-2. In addition, the preferential incidence of BALT was higher after MALP-2 application, in association with a bronchial diameter of 0.6-1 mm. The cellular analysis revealed no differences in the number of leukocyte subsets between the control and MALP-2 group. CONCLUSION: MALP-2 is a potent local stimulator and can be used to modulate BALT by repetitive inhalant treatment. The functional significance of enlarged or activated BALT has to be elucidated in future studies.

Adjuvants, Immunologic↗

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The pig as a model of developmental immunology.

There are many limitations to analyse the developing immune system in humans, thus there is need for experimental animal models to study the environmental influences during the ontogeny of the immune system. However risk assessment is difficult in using rodent models alone, especially as the intrauterine period of development is much shorter than that of humans. In addition to studies in dogs, the pig provides a variety of experimental approaches for developmental immunotoxicology. The gestation period is 115 days and the occurrence of the different lines of T and B lymphocytes in the blood and organs of the porcine embryo and fetus is well documented. Fetal porcine B cells represent a naive population developing without maternal idiotypic-antiidiotypic influences. The postnatal development is highly correlated to sufficient uptake of colostrum during the first 48 hours. Although many immunotoxicological experiments have been performed, there is a limited number of original publications about these studies. With the different strains of standard pigs and miniature pigs available and the rapid growing amount of immunological reagents, the pig represents an important experimental model for cost-effective studies in developmental immunotoxicology to analyse the risk of environmental hazards.

Age Factors↗

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Comparison of lymphocyte subsets, monocytes, and NK cells in three different lung compartments and peripheral blood in the rat.

Investigations on leukocyte populations in the lung have shown that lymphocytes are found in different anatomical compartments. Lymphocytes can be seen to a different extent in the lung interstitium, the epithelium and lamina propria of the bronchi, the bronchoalveolar space, and the marginal lung vascular bed. Previous studies focused on one compartment only, or a mixture of leukocytes from lung homogenates were prepared. This study compared cellular yields from the lung parenchyma, the bronchoalveolar space, and the perfusate of the lung vasculature of healthy male Lewis rats. All compartments were investigated in the same animal, and seven different lymphocyte subsets, monocytes, and natural killer (NK) cells were analyzed using flow cytometry. It was found that the perfusate contained a high proportion of CD4+ lymphocytes compared to the lung interstitium. A very high proportion of CD4+ lymphocytes in the bronchoalveolar lavage (BAL) expressed markers for "memory" T cells. Compared to the blood, the percentage of B and T cells was much lower in the perfusate, whereas the NK cells and monocytes were more frequent. Analysis of leukocyte subsets within all compartments revealed specific, distinguishable cell compositions. Extraction of interstitial lung cells was performed using two different methods. Enzymatic digestion of the lung tissue was compared with a mechanical disruption method. Hardly any differences were observed between the two methods regarding the distribution of lymphocyte subsets, monocytes, and NK cells. These data document the need to study more than one compartment before extrapolating to lymphocytes in the lung in general. Furthermore, changes in numbers of leukocytes and subsets can now be studied in models of lung infections and immune reactions, including the entry from the blood and intrapulmonary migration from one lung compartment to the other.

Animals↗

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Compartmentalization and kinetics of lymphoid cells in the lung.

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Animals↗