Published online before print July 15, 2003

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(Journal of Leukocyte Biology. 2003;74:558-563.)
© 2003 by Society for Leukocyte Biology

CCR4 blockade does not inhibit allergic airways inflammation

Dolores M. Conroy^*, Louise A. Jopling^*, Clare M. Lloyd^*, Martin R. Hodge, David P. Andrew, Timothy J. Williams^*, James E. Pease^* and Ian Sabroe^*,1

^* Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, United Kingdom; and
Millennium Pharmaceuticals Inc., Cambridge Massachusetts

¹Correspondence: Leukocyte Biology, Biomedical Sciences Division, Faculty of Medicine, Imperial College, South Kensington, London SW7 2AZ, UK. E-mail: i.sabroe{at}imperial.ac.uk

The CC chemokine receptor 4 (CCR4) shows selectivity for the recruitment of memory T cell subsets, including those of the T helper cell type 2 (Th2) phenotype. In humans, CCR4⁺ T cells are recruited to the asthmatic lung in response to allergen challenge; however, the contribution of this pathway to allergic disease remains uncertain. We therefore investigated the role of CCR4 in allergic airways inflammation in the guinea pig. Blockade of CCR4 with a specific antibody resulted in only minor changes in numbers of CCR4⁺ Th cells in the bronchoalveolar lavage fluid of allergen-challenged guinea pigs and failed to inhibit the generation of eotaxin/CC chemokine ligand (CCL)11 or macrophage-derived chemokine/CCL22 or the recruitment of inflammatory leukocytes to the lung. These data suggest that although CCR4 was originally proposed as a marker of Th2 status, antigen-specific Th2 cells are recruited to the lung predominantly by other pathways. This study casts doubts on the validity of CCR4 as a therapeutic target in the treatment of asthma.

Key Words: T lymphocytes • chemokines • allergy

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