CCL22 recruits CD4-positive CD25-positive regulatory T cells into malignant pleural effusion

Clin Cancer Res. 2009 Apr 1;15(7):2231-7. doi: 10.1158/1078-0432.CCR-08-2641. Epub 2009 Mar 24.

Abstract

Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory T cells infiltrating into the pleural space.

Experimental design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed.

Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space.

Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemokine CCL17 / analysis
  • Chemokine CCL22 / metabolism
  • Chemokine CCL22 / pharmacology
  • Chemokine CCL22 / physiology*
  • Chemotaxis
  • Humans
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Middle Aged
  • Pleural Effusion, Malignant / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Chemokine CCL17
  • Chemokine CCL22
  • Interleukin-2 Receptor alpha Subunit