Alveolar Epithelial Cells Block Lymphocyte Proliferation In Vitro without Inhibiting Activation

Abstract

In the face of constant exposure to inhaled antigens, precise local regulation of immune responses in the pulmonary alveolar space is essential to achieve a delicate balance between host defense and excessive immune responses that are incompatible with the primary physiologic function of the lung. We postulated that the cells of the alveolar epithelium may have an immunoregulatory role in the lung. Therefore, we have examined the effects of primary cultures of rat type II alveolar epithelial cells on lymphocyte proliferation and on the expression of a number of markers of T-cell activation. Monolayers of alveolar epithelial cells suppressed proliferation and DNA synthesis by concanavalin A-stimulated rat splenocytes. Suppression of [³H]thymidine incorporation was independent of the dose of mitogen and was also apparent when lymphocytes were stimulated with phorbol esters and calcium ionophore, suggesting that the effect was independent of cell surface binding of the lectin. Suppression was reversed 48 h after lectin-stimulated splenocytes were removed from co-culture with alveolar epithelial cells. Despite inhibition of lymphocyte proliferation, other markers of T-cell activation were induced normally in lymphocytes cultured with alveolar epithelial cells. Culture with alveolar epithelial cells did not inhibit the production of interleukin-2 by stimulated lymphocytes. Furthermore, by fluorescence-activated cell sorter analysis, equal proportions of stimulated lymphocytes in culture alone or with alveolar epithelial cell monolayers were induced to express receptors for interleukin-2 and for transferrin. Thus, stimulated splenocytes placed in culture with alveolar epithelial cells leave their resting state and express a number of T-cell activation markers while lymphocyte DNA replication is inhibited. These results suggest that the alveolar epithelium may have a previously undescribed role in local immunoregulation, suppressing lymphocyte clonal expansion in the alveolar space without inhibiting earlier lymphocyte activation responses.