Ovine skin-recirculating γδ T cells express IFN-γ and IL-17 and exit tissue independently of CCR7

gamma delta T cells continuously survey extralymphoid tissues, providing key effector functions during infection and inflammation. Despite their importance, the function and the molecules that drive migration of skin-recirculating gamma delta T cells are poorly described. Here we found that gamma delta T cells traveling in the skin-draining afferent lymph of sheep are effectors that produce IFN-gamma or IL-17 and express high levels of the skin- and inflammation-seeking molecule E-selectin ligand. Consistent with a role for chemokine receptor CCR7 in mediating T cell exit from extralymphoid tissues, conventional CD4 and CD8 T cells in skin-draining lymph were enriched in their expression of CCR7 compared to their skin-residing counterparts. In contrast, co-isolated T cells in skin or lymph lacked expression of CCR7, indicating that they use alternative receptors for egress. Skin-draining T cells were unresponsive to many cutaneous and inflammatory chemokines, including ligands for CCR2, CCR4, CCR5, CCR8, CCR10, and CXCR3, but showed selective chemotaxis toward the cutaneously expressed CCR6 ligand CCL20. Moreover, IL-17(+) gamma delta T cells were the most CCL20-responsive subset of gamma delta T cells. The data suggest that gamma delta T cells survey the skin and sites of inflammation and infection, entering via CCR6 and E-selectin ligand and leaving independent of the CCR7-CCL21 axis. (C) 2013 Elsevier B.V. All rights reserved.