Cutting Edge: Chemokine Receptor CCR4 Is Necessary for Antigen-Driven Cutaneous Accumulation of CD4 T Cells under Physiological Conditions

• Published in: Journal of Immunology 2007-03, Vol.178 (6), p.3358-3362
• Main Authors: Campbell, James J, O'Connell, Daniel J, Wurbel, Marc-Andre
• Format: Article
• Language: English
• Subjects: Animals; Antigens - immunology; Cell Movement - genetics; Cell Movement - immunology; Chemokine CCL17; Chemokines, CC - immunology; E-Selectin - immunology; Ligands; Mice; Mice, Knockout; Models, Immunological; Organ Specificity - genetics; Organ Specificity - immunology; Peritoneal Cavity; Receptors, CCR4; Receptors, Chemokine - deficiency; Receptors, Chemokine - immunology; Skin - immunology; Th1 Cells - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.6.3358

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.