Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells

In humans and rodents a population of naturally occurring CD4(+)CD25(+) T cells are suppressor T (CD25(+) Ts) cells, which are considered to maintain peripheral immunological tolerance. Recently, we have described a unique chemotactic response profile for human CD25(+) Ts cells, but their homing potential remains poorly defined. Here, we document a heterogeneous homing potential of human peripheral blood CD25(+) Ts cells consistent with their ability to mediate immunosuppression at distinct locations. Surprisingly, CD25(+) Ts cells are depleted of gut-homing integrin alpha(4)(+)beta(7)(+) T cells, while being enriched in skin-homing cutaneous lymphocyte antigen (CLA)(+) T cells. These findings document heterogeneous homing potential of peripheral blood-borne CD25(+) Ts cells with marked skewing for skin- versus gut-homing. Expression of CCR4 associates with both CD25 and CLA cell surface markers, being highest on CD4(+)CLA(+)CD25(+) T cells. Importantly, CD4(+)CD25(+) Ts cells isolated from human cord blood lack expression of CLA while expressing CCR4, suggesting intrinsic expression of CCR4 on CD25(+) Ts cells. These observations indicate that the increased expression of CCR4, which is proposed to guide CD25(+) Ts cells to DC, is an intrinsic feature of CD25(+) Ts cells.