Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis

Clin Exp Immunol. 2008 Apr;152(1):127-37. doi: 10.1111/j.1365-2249.2008.03609.x. Epub 2008 Feb 14.


In pulmonary sarcoidosis, the typical T helper 1-mediated immune response in the lungs has been proposed to be co-ordinated by regulatory T cells; however, their exact role needs to be clarified. We used real-time polymerase chain reaction to study genes involved in regulatory T cell functions in CD4+ T cells isolated from bronchoalveolar lavage fluid (BALF) of patients (n = 24) and healthy subjects (n = 7). The genes included the transcription factor forkhead box P3 (FoxP3), interleukin (IL)-10, transforming growth factor-beta1 and chemokine receptor 2 (CCR2). The same genes were also studied in isolated BALF CD4+ T cell receptor AV2S3+ and AV2S3(-) T cells of patients with lung-restricted AV2S3 T cell expansions (n = 12). Intracellular staining of the FoxP3 protein was performed additionally in 14 patients and nine healthy subjects. mRNA expression of FoxP3, CCR2 and IL-10 was decreased significantly in BALF CD4+ T cells of patients. Flow cytometric analysis of CD4+ T cells also demonstrated a decreased frequency of FoxP3+ cells in the BALF and blood of sarcoidosis patients as well as a reduced intensity (mean fluorescence intensity) of FoxP3 expression in BALF FoxP3+ cells of patients. BALF CD4+AV2S3+ T cells expressed significantly lower levels of FoxP3 and CCR2 mRNA versus BALF CD4+AV2S3- T cells. The main conclusion of our study is that there is a reduced expression of regulatory T cell associated genes in BALF CD4+ T cells in sarcoidosis. In addition, our data suggest an effector function of AV2S3+ lung-accumulated T cells in sarcoidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / genetics
  • Gene Expression / immunology
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Lung / immunology
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / genetics
  • Receptors, CCR2 / biosynthesis
  • Receptors, CCR2 / genetics
  • Sarcoidosis, Pulmonary / immunology*
  • Sarcoidosis, Pulmonary / physiopathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / metabolism*


  • CCR2 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger
  • Receptors, CCR2
  • Interleukin-10