Plasmacytoid DCs and Tolerance Induction There is growing evidence of the role of pDCs in immune tolerance. Defined originally by their capacity to secrete large amounts of type I interferons in response to viruses (23), pDCs also play an essential role in protection against inflammatory responses to harmless (inhaled) Ags (24). As discussed below, mature DCs can induce Treg responses in vitro (25,26), whereas in mice, prepDCs appear to be the principal cell type that facilitates allogeneic hematopoietic stem cell engraftment and the consequent induction of donor-specific skin graft tolerance (27). Moreover, donor-derived pre-pDCs infused 7 d before vascularized heart transplantation, significantly prolong subsequent graft survival in the absence of immunosuppressive therapy (28). As with mDCs (11), this effect is markedly enhanced by anti-CD154 monoclonal antibody (MAb) administration (29). Thus, it appears that both mDCs and pDCs can function as tolerogenic antigen-presenting cells (APC), and that maturation by itself is not the feature that distinguishes their immunogenic from their tolerogenic function. Indeed, maturation is more of a continuum than an “on-off” switch, and a “semi-mature” state, in which DCs are phenotypically mature, but remain poor producers or proinflammatory cytokines, has also been linked to tolerogenic function (18,30).