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CUTTING EDGE |
* Department of Dermatology, Brigham and Women’s Hospital, Boston, MA 02115;
Department of Dermatology and Department of Pathology, Harvard Medical School, Boston, MA 02115; and
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115
Dual expression of chemokine receptor CCR4 and E-selectin ligand is characteristic of skin-tropic CD4 T cells from blood, lymphoid organs, and the skin itself. A strong and specific correlation exists among CCR4, its ligand CCL17/TARC, and the cutaneous lymphocyte-homing process. Nevertheless, whether CCR4 function is required for skin-specific trafficking remains an open question, which we address in this study. We developed an Ag-specific, TCR-transgenic, murine CD4 T cell adoptive transfer model that induces a mixed Th1 and Th17 cutaneous response. Within the hosts, both CCR4+/+ and CCR4–/– donor CD4 T cells contribute equally well to the circulating E-selectin ligand+ pool in response to Ag. However, only CCR4+/+ donor cells accumulate efficiently within the skin. CCR4–/– cells home normally to the peritoneum, showing that they do not have a general defect in lymphocyte trafficking. We conclude that under physiological conditions, CCR4 is a nonredundant, necessary component of skin-specific lymphocyte trafficking.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant R01AI046784 (to J.J.C.) and an Award from the Crohn’s and Colitis Foundation of America (to M.-A.W.).
2 Address correspondence and reprint requests to Dr. James J. Campbell, Ph.D., Brigham and Women’s Hospital, Department of Dermatology, 221 Longwood Avenue, EBRC 511, Boston, MA 02115. E-mail address: jcampbell{at}rics.bwh.harvard.edu
3 Abbreviations used in this paper: DNFB, 2,4-dinitro-1-fluorobenzene; CT, cholera toxin; LN, lymph node; DLN, draining LN; E-lig, E-selectin ligand; WT, wild type; BM, bone marrow.
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