title: T-cell activation profiles in different granulomatous interstitial lung diseases--a role for CD8+CD28(null) cells?
abstract: Lymphocytes play a crucial role in lung inflammation. Different interstitial lung diseases may show distinct lymphocyte activation profiles. The aim of this study was to examine the expression of a variety of activation markers on T lymphocyte subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with different granulomatous interstitial lung diseases and healthy controls. Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven patients with hypersensitivity pneumonitis and 24 healthy controls were analysed. Lymphocyte activation status was determined by flow cytometry. Lymphocytes were stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR expression on BALF CD8+ lymphocytes was different in patients with hypersensitivity pneumonitis and sarcoidosis patients with parenchymal involvement. This BALF lymphocyte phenotype correlated with carbon monoxide diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2 = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I versus stage II and higher, P = 0.006) and with the need for corticosteroid treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null) cells might be a new biomarker for disease severity but needs further investigation.
authors.affiliation: Center for Interstitial Lung diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Heron
authors.forename: A M E
authors.initials: AM
authors.lastname: Claessen
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
authors.forename: J M M
authors.initials: JM
authors.lastname: van den Bosch
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000097:blood / Q000276:immunology / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018106:CD28 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002248:Carbon Monoxide / Q000378:metabolism; D005260:Female; D006099:Granuloma / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D011859:Radiography; D017565:Sarcoidosis, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D018106:CD28 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D002248:Carbon Monoxide