Article

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

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 01/2009; 123(1):67-73.e3. DOI: 10.1016/j.jaci.2008.09.049
Source: PubMed

ABSTRACT 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.
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.
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.
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.
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.

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    • "l outcome by an en - dogenous biased agonist of a chemokine receptor . Data obtained in humans has been corroborated to a certain extent by rodent models of allergic airways disease . Mikhak et al showed that antigen - specific Th2 cells adoptively transferred from CCR4 - deficient mice fail to traffic in significant numbers to the allergic lung ( Mikhak et al . , 2009 ) . Similarly , antibody neutraliza - tion of either CC17 or CCL22 proved to be effective in reducing leukocyte recruitment to the lung and associated parameters of inflammation , following allergen challenge ( Kawasaki et al . , 2001 ; Lloyd et al . , 2000 ) . In contrast to these studies , ovalbumin chal - lenged CCR4 null mice were n"
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