Neuropilin-1: a surface marker of regulatory T cells

CD4(+)CD25(+) regulatory T cells (T-reg cells) control immune responsiveness to a large variety of antigens. The isolation and therapeutic manipulation of T-reg cells requires the use of reliable surface receptors that are selectively up-regulated in T-reg cells. On the basis of global gene expression studies, we identified neuropilin-1 (Nrp1) as a specific surface marker for CD4(+)CD25(+) T-reg cells. Nrp1, a receptor involved in axon guidance, angiogenesis, and the activation of T cells, is constitutively expressed on the surface of CD4(+)CD25(+) T-reg cells independently of their activation status. In contrast, Nrp1 expression is down-regulated in naive CD4(+)CD25(-) T cells after TCR stimulation. Furthermore, CD4(+)Nrp1(high) T cells express high levels of Foxp3 and suppress CD4(+)CD25(-) T cells. Thus, Nrp1 constitutes a useful surface marker to distinguish T-reg cells from both naive and recently activated CD4(+)CD25(+) nonregulatory T cells.