A neuronal receptor, neuropilin-I, is essential for the initiation of the primary immune response

The initiation of a primary immune response requires contact between dendritic cells (DCs) and resting T cells. However, little is known about the proteins that mediate this initial contact. We show here that neuropilin-I, a receptor involved in axon guidance, was expressed by human DCs and resting T cells both in vitro and in vivo. The initial contact between DCs and resting T cells led to neuropilin-I polarization on T cells. DCs and resting T cells specifically bound soluble neuropilin-I, and resting T cells formed clusters with neuropilin-I-transfected COS-7 cells in a neuropilin-I-dependent manner. Functionally, preincubation of DCs or resting T cells with blocking neuropilin-I antibodies inhibited DC-induced proliferation of resting T cells. These data suggest that neuropilin-I mediates interactions between DCs and T cells that are essential for initiation of the primary immune response and show parallels between the nervous and immune systems.