Alveolar epithelial cells block lymphocyte proliferation in vitro without inhibiting activation.
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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Paine
R
R
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0360.
Mody
C H
CH
Chavis
A
A
Spahr
M A
MA
Turka
L A
LA
Toews
G B
GB
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D011650:Pulmonary Alveoli / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D003208:Concanavalin A; D007213:Indomethacin