title: CD27 expression on CD4+ T cells differentiates effector from regulatory T cell subsets in the lung.
abstract: Beryllium exposure in the workplace can result in chronic beryllium disease, a granulomatous lung disorder characterized by CD4(+) T cell alveolitis and progressive lung fibrosis. A large number of the CD4(+) T cells recruited to the lung in chronic beryllium disease recognize beryllium in an Ag-specific manner and express Th1-type cytokines following T cell activation. Beryllium-responsive CD4(+) T cells in the bronchoalveolar lavage (BAL) express an effector memory T cell phenotype and recognize beryllium in a CD28-independent manner. In this study, we show that the majority of beryllium-responsive CD4(+) T cells in BAL have lost CD27 expression, whereas a subset of beryllium-responsive cells in blood retains expression of this costimulatory molecule. In addition, loss of CD27 on BAL CD4(+) T cells inversely correlates with markers of lung inflammation. A small population of BAL CD4(+) T cells retains CD27 expression, and these CD4(+)CD27(+) T cells contain the FoxP3-expressing, naturally occurring regulatory T (T(reg)) cell subset. Coexpression of CD27 and CD25 identifies the majority of FoxP3-expressing T(reg) cells in blood and BAL, and these cells express potent suppressor function. Taken together, these findings suggest that CD27 is differentially expressed between effector T cells from the inflamed lung and can be used in conjunction with CD25 to isolate T(reg) cells and assess their functional capacity in an ongoing adaptive immune response in a target organ.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mack
authors.forename: Allison M
authors.initials: AM
authors.lastname: Lanham
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
mesh_terms: D000328:Adult; D000368:Aged; D001608:Beryllium / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D006801:Humans; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis*
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D001608:Beryllium