title: Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response.
abstract: Beryllium exposure can lead to the development of beryllium-specific CD4+ T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4+ T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4+ T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the 2 types of responses was poor. We hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4+ T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, we found a direct correlation between the percentage of beryllium-specific CD4+ T(EM) cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4+ T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement.
authors.affiliation: Division of Clinical Immunology, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. andrew.fontenot@uchsc.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sullivan
authors.forename: Fenneke G
authors.initials: FG
authors.lastname: Joslin
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
mesh_terms: D000368:Aged; D001607:Berylliosis / Q000097:blood / Q000276:immunology*; D001608:Beryllium / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D001608:Beryllium