Brief Definit ive Report The longstanding Langerhans cell (LC) para-

Villadangos, 2004) holds that LCs acquire skin-associated antigens and present them to T cells upon migrating to skin-draining lymph nodes. However, a series of recent studies using trans-genic mouse models has failed to clearly dem-onstrate a critical contribution of LCs in the induction of immunity to percutaneous anti-gens in vivo. LCs were dispensable for antiviral immu-nity in a herpes simplex virus skin scarification model (Allan et al., 2003), and mouse models in which LCs were transiently or constitutively depleted showed that they were not essential for eliciting hapten-induced contact hypersensitiv-ity (Kaplan et al., 2005; Kissenpfennig et al., 2005; Bennett et al., 2007). It is possible that LCs are tolerogenic, but this may depend on the na-ture of the antigen (e.g., foreign or self), route of antigen exposure (e.g., through the epidermis or directly into the dermis), and presence or absence of environmental cues, including inter-actions with pathogens (Kautz-Neu et al., 2011). We recently reported that LCs induced IgG1 (Th2) responses to gene gun–immunized bacterial antigens and that skin DC subsets had distinct roles in inducing humoral responses (Nagao et al., 2009). Although this experimenta