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J Allergy Clin Immunol. 2009 Jan;123(1):67-73.e3. doi: 10.1016/j.jaci.2008.09.049. Epub 2008 Dec 4.

Contribution of CCR4 and CCR8 to antigen-specific T(H)2 cell trafficking in allergic pulmonary inflammation.

Author information

  • 1Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

BACKGROUND:

Recruitment of antigen-specific T(H)2 cells into the lung is critical for the development of allergic airway inflammation. Although CCR4 and CCR8 are preferentially expressed on T(H)2 cells and CCR4, CCR8, and CXCR3 ligands are increased in asthma, the specific relative contribution of these receptors to antigen-specific T(H)2 cell trafficking into the allergic lung is not known.

OBJECTIVE:

To determine the relative contribution of the chemokine receptors CCR4, CCR8, and CXCR3 to antigen-specific T(H)2 cell trafficking in a murine model of allergic pulmonary inflammation.

METHODS:

We used adoptive transfer experiments to compare the trafficking of wild-type antigen-specific T(H)2 cells with antigen-specific T(H)2 cells deficient in CCR4, CCR8, or CXCR3.

RESULTS:

CCR4-deficient antigen-specific T(H)2 cells failed to traffic efficiently into the lung and the airways. In contrast, CCR8-deficient antigen-specific T(H)2 cells accumulated in these sites. Trafficking of CXCR3-deficient antigen-specific T(H)2 cells and CCR4-deficient and CCR8-deficient antigen-specific T(H)1 cells were comparable to their wild-type counterparts. Approximately 60% of IL-4-producing antigen-specific T cells expressed CCR4. Disruption of CCR4-mediated antigen-specific T(H)2 cell trafficking decreased the levels of T(H)2-type cytokines in the airways and reduced airway eosinophilia and mucus production.

CONCLUSIONS:

Our study demonstrates that CCR4 is required for the efficient entry of antigen-specific T(H)2 cells into the lung and the airways in a murine model of allergic pulmonary inflammation.

PMID:
19062085
[PubMed - indexed for MEDLINE]
PMCID:
PMC2782398
Free PMC Article

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