A role for TGF-beta in the suppression by murine bronchoalveolar cells of lung dendritic cell initiated immune responses.
Effective pulmonary immune responses likely require both local antigen presenting cells (APC) and regulatory suppressor cells. Bronchoalveolar cells (BAC), which consist primarily of alveolar macrophages (AM), are poor APC in most species and are often suppressive. However, dendritic cell (DC)-enriched populations from both lung interstitium and BAC have potent APC activity as measured by their capacity to stimulate both alloantigen and antigen-induced lymphoproliferative T cell responses. To determine if BAC could down-regulate pulmonary immune responses, BAC were mixed with DC-enriched loosely adherent lung interstitial cells (LAd) in a mixed leukocyte reaction (MLR). With high numbers of BAC, MLRs were consistently suppressed and suppression was partially reversed by the addition of indomethacin and catalase. Supernatants from BAC cultured with either syngeneic or allogeneic T lymphocytes in the presence of indomethacin and catalase markedly suppressed an MLR, while supernatants from BAC cultured alone were inconsistently suppressive. Antibodies to TGF-beta completely reversed the BAC-T cell supernatant-induced suppression of the MLR. However, TGF-beta antibody only partially reversed BAC-induced suppression when BAC were added directly to MLR cultures that contained indomethacin and catalase, suggesting that, in addition to TGF-beta, prostaglandins, and H2O2, BAC in culture with LAd and allogeneic T cells also produced short-lived suppressive factors and/or mediated suppression by direct cell contact. Thus, resident BAC likely utilize multiple mechanisms including TGF-beta secretion to suppress intra-alveolar immune responses initiated by lung DC.
Lipscomb
M F
MF
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.
Pollard
A M
AM
Yates
J L
JL
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
D016212:Transforming Growth Factor beta