The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells

Lymphocytes that are responsible for regional (tissue-specific) immunity ho me from the blood to the intestines, inflamed skin or other sites through a multistep process involving recognition of vascular endothelial cells and extravasation(1). Chemoattractant cytokine molecules known as chemokines(2) regulate this lymphocyte traffic, in part by triggering arrest (stopping) of lymphocytes rolling on endothelium(3-5). Here we shaw that many systemic memory T cells in blood carry the chemokine receptor CCR4 (ref. 6) and the refore respond to its ligands, the chemokines TARC and MDC. These cells inc lude essentially all skin-homing cells expressing the cutaneous lymphocyte antigen and a subset of other systemic memory lymphocytes; however, intesti nal (alpha 4 beta 7(+)) memory and naive T cells respond poorly. Immunohist ochemistry reveals anti-TARC reactivity of venules and infiltration of many CCR4(+) lymphocytes in chronically inflamed skin, but not in the gastroint estinal lamina propria. Moreover, TARC induces integrin-dependent adhesion of skin (but not intestinal) memory T cells to the cell-adhesion molecule I CAM-1, and causes their rapid arrest under physiological now. Our results s uggest that CCR4 and TARC are important in the recognition of skin vasculat ure by circulating T cells and in directing lymphocytes that are involved i n systemic as opposed to intestinal immunity to their target tissues.