A factor secreted by a human pulmonary alveolar epithelial-like cell line blocks T-cell proliferation between G1 and S phase.
Because the pulmonary alveolar space is both the site of gas exchange for respiration and a portal of entry for foreign antigen, immunologic interactions within that space must be meticulously controlled. Alveolar epithelial cells are ideally situated to play a role in immune regulation within the alveolar space. We have used A549 cells, a cell line that is derived from a human alveolar cell carcinoma and that has been used as a model for alveolar type II epithelial cells, to examine the potential role of alveolar epithelial cells in local pulmonary immune regulation. Medium conditioned by confluent monolayers of A549 cells suppressed proliferation by human peripheral blood mononuclear cells (PBMC) stimulated with lectin, anti-CD3 antibodies, calcium ionophore and phorbol ester, or in a mixed leukocyte reaction. PBMC that had been incubated in and then removed from A549-conditioned medium went on to proliferate normally. Because the suppressive effect was abrogated by heating or acidification and was not blocked by neutralizing antibody to transforming growth factor-beta 1, this effect could not be attributed to transforming growth factor-beta. The factor mediating this effect has an approximate molecular weight of 70,000 D by gel filtration chromatography. Nonalveolar, pulmonary carcinoma cell lines did not exert this immunosuppressive influence nor did the alveolar epithelial cells inhibit proliferation by the transformed, Jurkat, T-cell line. Cell cycle analysis demonstrated that PBMC exposed to A549 cell-conditioned medium failed to enter S phase after mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Paine
R
R
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor 48109-0360.
Chavis
A
A
Gaposchkin
D
D
Christensen
P
P
Mody
C H
CH
Turka
L A
LA
Toews
G B
GB
D001685:Biological Factors / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism*; D016196:S Phase; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014407:Tumor Cells, Cultured
D001685:Biological Factors; C067763:epithelium-derived inhibitory factor