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Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response
Andrew P. Fontenot, … , Lee S. Newman, Brian L. Kotzin
Andrew P. Fontenot, … , Lee S. Newman, Brian L. Kotzin
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2886-2893. https://doi.org/10.1172/JCI24908.
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Research Article Immunology Article has an altmetric score of 12

Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response

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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+ TEM 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

Andrew P. Fontenot, Brent E. Palmer, Andrew K. Sullivan, Fenneke G. Joslin, Cara C. Wilson, Lisa A. Maier, Lee S. Newman, Brian L. Kotzin

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Figure 4

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Maturation phenotype of beryllium-specific and SEB-responsive CD4+ T cel...
Maturation phenotype of beryllium-specific and SEB-responsive CD4+ T cells from 12 CBD patients (filled triangles) and 3 BeS subjects (open triangles). (A and B) The percentage of beryllium-specific IFN-γ+ (A, left) and IL-2+ (B, left) CD4+ T cells displaying a particular maturation phenotype as determined by the expression of CCR7 and CD45RA is shown. In addition, the percentage of SEB-responsive IFN-γ+ (A, right) and IL-2+ (B, right) CD4+ T cells displaying a particular maturation phenotype based on the expression of CCR7 and CD45RA is shown. The median percentage is shown as a solid line. (C) Longitudinal studies of the percentage of beryllium-specific CD4+ T cells expressing a TEM cell phenotype over time. PBMCs were obtained from 4 CBD subjects at time intervals ranging from 7 to 14 months after the initial evaluation.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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