Reviews and feature articleContribution of CCR4 and CCR8 to antigen-specific TH2 cell trafficking in allergic pulmonary inflammation
Section snippets
Mice
Thy1.1+ OTII, Thy1.2+ OTII, and CXCR3−/− mice were obtained as previously described.28 CCR8−/− mice were a gift from Sergio A. Lira (Mount Sinai School of Medicine, New York, NY).17 CCR4−/− and C57BL/6 mice were purchased from the Jackson Laboratory. All mice were in the C57BL/6 background. CCR4−/−OTII, CXCR3−/−OTII, CCR8−/−OTII, and Thy1.1+Thy1.2+ mice were bred in our laboratory. Chemokine receptor-deficient OTII mice were generated by breeding male OTII mice with female chemokine
CCR4 deficiency diminishes antigen-specific TH2 cell trafficking into the lung and the airways, whereas CXCR3 and CCR8 deficiency are not associated with a trafficking defect
To study the relative contribution of CCR4, CCR8, and CXCR3 to the trafficking of antigen-specific TH2 cells, we compared the homing of wild-type OTII TH2 cells, which are transgenic for the T-cell receptor recognizing ovalbumin peptide323-339, with the homing of OTII TH2 cells deficient in CCR4, CCR8, or CXCR3 into the lung and the airways in vivo, using a competitive adoptive transfer model.32 We chose an adoptive transfer approach to isolate the effect of deficiency in CCR4, CCR8, or CXCR3
Discussion
In this study, we have delineated the role of CCR4, CCR8, and CXCR3 in antigen-specific TH2-cell trafficking. We have shown that CCR4 deficiency decreases antigen-specific TH2-cell trafficking into the allergic lung, CXCR3 deficiency has no impact, and CCR8 deficiency leads to an accumulation of these cells. The roles of CCR4 and CCR8 were specific for antigen-specific TH2 cells because antigen-specific TH1-cell trafficking was not affected by CCR4 or CCR8 deficiency.
There are conflicting
Acknowledgments
We thank Sergio Lira (Mount Sinai, New York, NY) for the CCR8−/− mouse, Craig Gerard (Children's Hospital, Boston, Mass) for the CXCR3−/− mouse, and Daniel Campbell (Benaroya Research Institute, Seattle, Wash) for the CCL22-IgG fusion protein DNA construct.
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Supported by the National Institutes of Health (R37-AI40618 to A.D.L. and K08AI67519 to Z.M.).
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.