Pulmonary T(H)2 response in Pseudomonas aeruginosa-infected patients with cystic fibrosis

J Allergy Clin Immunol. 2006 Jan;117(1):204-11. doi: 10.1016/j.jaci.2005.09.023. Epub 2005 Nov 28.

Abstract

Background: Pseudomonas aeruginosa infection determines the course of cystic fibrosis (CF) lung disease. Studies in human peripheral blood indicate that P aeruginosa infection is associated with a predominant T(H)2 immune response, whereas T(H)1 responses are accompanied by a better pulmonary outcome.

Objective: Analyses of peripheral blood may not correspond directly with the local pulmonary immune response. Therefore, we asked whether the T(H)1/T(H)2 response is altered in bronchoalveolar lavage fluid from P aeruginosa-infected patients with CF.

Methods: Bronchoalveolar lavage fluid was obtained from 12 patients with CF chronically infected with P aeruginosa, 11 noninfected patients with CF, and 8 healthy controls. Pulmonary CXCR3(+) (T(H)1) and CCR4(+) (T(H)2) expressing CD4(+) and CD8(+) lymphocytes were quantified by flow cytometry. Levels of T(H)1-associated (IL-2, IFN-gamma, IFN-gamma inducible T cell-alpha chemoattractant, Monokine induced by IFN-gamma, IFN-gamma inducible protein of 10 kd) and T(H)2-associated (IL-4, IL-5, IL-10, thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine) cytokines and chemokines and a panel of proinflammatory molecules were quantified at the protein level. Chemokines mRNA levels were assessed by real time RT-PCR.

Results: P aeruginosa-infected patients with CF had significantly higher levels of pulmonary CCR4(+)CD4(+) (T(H)2) cells, IL-4, IL-13, and TARC and lower levels of IFN-gamma compared with noninfected patients with CF and healthy controls. Bronchoalveolar lavage fluid levels of IL-4, IL-13, and TARC correlated inversely with FEV(1) in P aeruginosa-infected patients with CF.

Conclusion: These results reveal the prevalence of a pulmonary T(H)2 immune response in P aeruginosa-infected patients with CF. The modulation of the pulmonary T(H)2 response in P aeruginosa infection may be an option for the treatment of P aeruginosa lung disease in patients with CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chemokine CCL17
  • Chemokines, CC / analysis
  • Child
  • Cystic Fibrosis / immunology*
  • Female
  • Humans
  • Interleukin-13 / analysis
  • Interleukin-4 / analysis
  • Lung / immunology*
  • Male
  • Pseudomonas Infections / immunology*
  • Receptors, CCR4
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis
  • Th1 Cells / immunology
  • Th2 Cells / immunology*

Substances

  • CCL17 protein, human
  • CCR4 protein, human
  • CXCR3 protein, human
  • Chemokine CCL17
  • Chemokines, CC
  • Interleukin-13
  • Receptors, CCR4
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Interleukin-4