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

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+ 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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Frequency of beryllium-specific CD4+ T cells in blood and beryllium-indu...
Frequency of beryllium-specific CD4+ T cells in blood and beryllium-induced CD4+ T cell proliferation. (A) Representative examples of beryllium-induced intracellular IFN-γ expression from the blood of 2 CBD patients are shown (left density plots). The number in the top right quadrant of the density plots indicates the percentage of CD4+ T cells expressing IFN-γ after short-term exposure to 1 × 10–4 M BeSO4. Beryllium-induced proliferation as detected by loss of CFSE labeling (right density plots) after exposure to 1 × 10–4 M BeSO4 for 7 days in culture for the same 2 CBD patients is shown. After gating on CD4+ T cells, loss of CFSE expression in relation to the costimulatory molecule CD28 is shown. The number in the top left quadrant of the density plots indicates the percentage of CD4+ T cells proliferating after 7 days of culture in the presence of 1 × 10–4 M BeSO4. (B) Correlation of lymphoproliferation as measured by loss of CFSE expression on CD4+ T cells and beryllium-induced IFN-γ (left) and IL-2 expression (right) is shown.