Identification of a Novel Proinflammatory

gd T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human gd cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive Vg9Vd2 T cells, which is rapidly recruited into perturbed human skin. Vg9Vd2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF-a– and IFN-g–dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vg9Vd2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vg9Vd2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of Vg9Vd2 T cells in psoriatic skin, these data indicate redistribution of Vg9Vd2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory gd T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. I n murine skin, the function of gd T cells has been investigated extensively. Mouse epidermis contains large numbers of dendritic Vg5Vd1 + T cells, appropriately termed dendritic epidermal T cells (DETC) (1). DETC have been shown to participate in immunoregulation of the skin (2, 3) and to protect against epithelial malignancies (4, 5). Furthermore, gd T cells in murine skin may produce growth factors that maintain epidermal integrity (6, 7). In contrast to mouse skin, gd T cells are rare in healthy human skin, and an equivalent of mouse DETC does not appear to exist. Approximately 2–9% of all dermal and 1–10% of all epidermal T cells are gd T cells (8–14). Vd1 T cells are considered to be the primary gd T cell subset in skin playing a role in skin cancer immune surveillance (14) and wound healing (13), whereas a direct association of Vg9Vd2 T cells with cutaneous immunology has to date been lacking. Because gd + T cells are less frequent in human skin compared with the frequency of DETC in murine skin, a key question is whether they perform a similar lymphoid stress–surveillance role as their murine counterpart (15). Psoriasis is a common chronic inflammatory skin disease with a significant genetic disease susceptibility component (16, 17). Although …