IgA-Driven Antibacterial Activity AgainstStreptococcus pneumoniaeby Mouse Lung Lymphocytes

Publisher Website
Google Scholar
Abstract
To investigate the role of lung lymphocytes (LL) in the local defense mechanisms. We studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using Streptococcus pneumoniae type 3 as target. In parallel, natural killer (NK) activity; against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (> 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2-, aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T-cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism. Thus, IgA immunoglobulins might participates in the defense of the lung mucosa against bacterial infections by arming these lymphocytes, as well as AM and other phagocytic cells, to become specifically cytotoxic against bacteria.