Local proliferation contributes to lymphocyte numbers in normal lungs

Lymphocytes in the bronchoalveolar lavage fluid (BAL) are increased in many lung diseases, which might be an indicator for protective reactions or pathology. Higher lymphocyte numbers at distinct organ sites may be due to a number of reasons such as increased entry, increased proliferation, reduced apoptosis or reduced exit. It is not known whether lymphocyte numbers are influenced by local proliferation in the healthy lung. Therefore, the proliferation of lymphocytes was studied in vivo in different lung compartments of healthy rats: the marginal vascular pool, the interstitial pool and the bronchoalveolar pool. Bromodeoxyuridine (BrdU) was used as an S-phase proliferation marker. The cells were obtained 1 h and 24 h after i.v. injection of BrdU. The labeled cells and their phenotypes were determined by immunocytochemistry, since it was not possible to use flow cytometry because of the low numbers. In the lung compartments 0.7-1.5% of all nucleated cells were found to be BrdU+, whereas 24 h later this increased to 3.2-5.7%. The frequency of BrdU+ T cells was significantly higher in the lung compartments compared to the blood, with the maximum in the marginal vascular pool. Local proliferation of lymphocytes involved mainly CD8+ T cells. Thus, local proliferation plays a role in the number and composition of lymphocytes in the healthy normal lung.