Treatment with imatinib results in reduced IL-4-producing T cells, but increased CD4(+) T cells in the broncho-alveolar lavage of patients with systemic sclerosis

Clin Immunol. 2011 Dec;141(3):293-303. doi: 10.1016/j.clim.2011.08.010. Epub 2011 Sep 5.


T cells, particularly those producing IL-4, are implicated in inflammation-mediated fibrosis. In our phase I/IIa open-label pilot study in 15 patients with scleroderma-interstitial lung disease (SSc-ILD), high-dose imatinib treatment showed modest improvement in lung function and skin score, but with several adverse events. Here, we investigated T cell phenotype and cytokine production in bronchoalveolar lavage (BAL) from patients enrolled in this trial. We found that IL-4(+) T cells showed a stronger correlation with ground glass opacity (GGO) than fibrosis scores on lung high-resolution computer tomography scans. Frequencies of IL-4(+) T cells also discriminated patients with high (≥20) versus low (<20) GGO scores. Functional annotation clustering of proteins that correlated with T cells identified two major clusters that belonged to immune/inflammatory and wounding response. Repeat analyses after 1 year of treatment in 10 BAL samples, one each from the right middle and lower lobes of lung from 5 patients, showed that post-imatinib, IL-4(+) T cells were profoundly reduced but CD4(+) T cells increased, except in one patient who showed worsening of SSc-ILD. Post-imatinib increase in CD4(+) T cells correlated with soluble ICAM-3 and PECAM-1 levels in BAL, which associated with the lack of worsening in SSc-ILD. Thus, imatinib might confer its therapeutic effect in fibrosis via re-directing T cell responses from type 2 to other, non-type 2 cytokine producing CD4(+) T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, CD / immunology
  • Benzamides
  • Bronchoalveolar Lavage Fluid / immunology*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / immunology
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Imatinib Mesylate
  • Interleukin-4 / immunology*
  • Lung / diagnostic imaging
  • Lung / immunology
  • Male
  • Middle Aged
  • Pilot Projects
  • Piperazines / therapeutic use*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Platelet Endothelial Cell Adhesion Molecule-1 / immunology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Radiography
  • Scleroderma, Systemic / diagnostic imaging
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / immunology


  • Antigens, CD
  • Benzamides
  • Cell Adhesion Molecules
  • ICAM3 protein, human
  • IL4 protein, human
  • Piperazines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Interleukin-4
  • Imatinib Mesylate