Pulmonary T_H2 response in Pseudomonas aeruginosa–infected patients with cystic fibrosis

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_H2 immune response, whereas T_H1 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_H1/T_H2 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_H1) and CCR4⁺ (T_H2) expressing CD4⁺ and CD8⁺ lymphocytes were quantified by flow cytometry. Levels of T_H1-associated (IL-2, IFN-γ, IFN-γ inducible T cell-α chemoattractant, Monokine induced by IFN-γ, IFN-γ inducible protein of 10 kd) and T_H2-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_H2) cells, IL-4, IL-13, and TARC and lower levels of IFN-γ compared with noninfected patients with CF and healthy controls. Bronchoalveolar lavage fluid levels of IL-4, IL-13, and TARC correlated inversely with FEV₁ in P aeruginosa–infected patients with CF.

Conclusion

These results reveal the prevalence of a pulmonary T_H2 immune response in P aeruginosa–infected patients with CF. The modulation of the pulmonary T_H2 response in P aeruginosa infection may be an option for the treatment of P aeruginosa lung disease in patients with CF.

Key words: Cystic fibrosis, Pseudomonas aeruginosa, bronchoalveolar lavage fluid, TARC, MDC, CCR4, T_H1/T_H2, cytokines

Abbreviations used: BAL, Bronchoalveolar lavage, BALF, Bronchoalveolar lavage fluid, CF, Cystic fibrosis, G-CSF, Granulocyte colony-stimulating factor, IP-10, IFN-γ inducible protein of 10 kd, ITAC, IFN-γ inducible T cell-α chemoattractant, MCP, Macrophage chemotactic protein, MDC, Macrophage-derived chemokine, Mig, Monokine induced by IFN-γ, MIP, Macrophage inflammatory protein, OdDHL, N-(3-oxododecanoyl)-homoserine lactone, TARC, Thymus and activation-regulated chemokine, Tc, T cytotoxic cell type