title: Target organ localization of memory CD4(+) T cells in patients with chronic beryllium disease.
abstract: Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace, and it remains an important public health concern. Evidence suggests that CD4(+) T cells play a critical role in the development of this disease. Using intracellular cytokine staining, we found that the frequency of beryllium-specific CD4(+) T cells in the lungs (bronchoalveolar lavage) of 12 CBD patients ranged from 1.4% to 29% (mean 17.8%), and these T cells expressed a Th1-type phenotype in response to beryllium sulfate (BeSO(4)). Few, if any, beryllium-specific CD8(+) T cells were identified. In contrast, the frequency of beryllium-responsive CD4(+) T cells in the blood of these subjects ranged from undetectable to 1 in 500. No correlation was observed between the frequency of beryllium-responsive bronchoalveolar lavage (BAL) CD4(+) T cells as detected by intracellular staining and lymphocyte proliferation in culture after BeSO(4) exposure. Staining for surface marker expression showed that nearly all BAL T cells exhibit an effector memory cell phenotype. These results demonstrate a dramatically high frequency and compartmentalization of antigen-specific effector memory CD4(+) cells in the lungs of CBD patients. These studies provide insight into the phenotypic and functional characteristics of antigen-specific T cells invading other inaccessible target organs in human disease.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. andrew.fontenot@uchsc.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Canavera
authors.forename: Laia
authors.initials: L
authors.lastname: Gharavi
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
mesh_terms: D001607:Berylliosis / Q000276:immunology* / Q000473:pathology; D001608:Beryllium / Q000276:immunology / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; C020711:beryllium sulfate; D001608:Beryllium