Deficient and dysfunctional regulatory T cells in the lungs of chronic beryllium disease subjects

Am J Respir Crit Care Med. 2010 Jun 1;181(11):1241-9. doi: 10.1164/rccm.201001-0025OC. Epub 2010 Mar 18.


Rationale: Chronic beryllium disease (CBD) is a CD4(+) T cell-mediated disorder characterized by persistent lung inflammation. Naturally occurring regulatory T (T(reg)) cells modulate adaptive immune responses. The role of this T-cell subset in beryllium-induced lung disease is unknown.

Objectives: The aim of this study was to determine whether dysfunctional T(reg) cells in the lung contribute to the "unchecked" inflammatory response that characterizes CBD.

Methods: Using blood and bronchoalveolar lavage (BAL) cells from normal control subjects and individuals with beryllium-induced disease, we determined the frequency and function of naturally occurring T(reg) cells.

Measurements and main results: A significantly decreased percentage and expression of FoxP3 in BAL CD4(+) T cells from CBD patients compared with beryllium-sensitized subjects was seen, and the percentage of FoxP3-expressing CD4(+) T(reg) cells in BAL inversely correlated with disease severity. In contrast to blood T(reg) cells derived from beryllium-sensitized subjects and patients with CBD that completely suppressed blood responder T-cell proliferation, BAL FoxP3-expressing T(reg) cells from patients with CBD are unable to suppress anti-CD3-mediated BAL T-cell proliferation. Mixing studies showed that blood T(reg) cells are capable of suppressing autologous BAL responder T cells. Conversely, BAL CD4(+) T(reg) cells are incapable of suppressing blood T cells, confirming that the failure of BAL T(reg) cells to suppress T-cell proliferation is caused by a dysfunctional T(reg) cell subset and not by resistance of BAL effector T cells to suppression.

Conclusions: These findings suggest that the deficient and dysfunctional T(reg) cells in the lung of patients with CBD contribute to the persistent inflammatory response in this disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology
  • Berylliosis / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • CD3 Complex / immunology
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Chronic Disease
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lung / immunology
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism*


  • Antibodies, Monoclonal
  • CD3 Complex
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit