Langerin+ Dermal DC, but Not Langerhans Cells, Are Required for Effective CD8-Mediated Immune Responses after Skin Scarification with Vaccinia Virus

Skin scarification (s.s.) with vaccinia virus (VACV) is essential for generation of an optimal protective T-cell memory immune response. Dendritic cells (DCs), which are professional antigen-presenting cells, are required for naive T-cell priming and activation. At least three subsets of skin-resident DC have been identified: Langerhans cells (LCs), dermal Langerin + DC (Lang + dDC), and dermal Langerin − DC (Lang − dDC). Using Langerin-diphtheria toxin receptor mice and established mouse model of VACV delivered by s.s., we demonstrated that Lang + dDC, but not LC, are absolutely required for the induction of a rapid and robust antigen-specific CD8 + T-cell response after s.s. with VACV. The depletion of Lang + dDC led to a significant delay in the priming and proliferation of antigen-specific CD8 + T cells. Moreover, CD8 + T cells generated after VACV s.s. in the absence of Lang + dDC lacked effector cytotoxic functions both in vitro and in vivo . While s.s.-immunized wild-type and LC-depleted mice controlled the progression of OVA 257–264 expressing T-cell lymphoma EG7 (injected intradermally), the depletion of Lang + dDC led to rapid lymphoma progression and mortality. These data indicate that of all skin DC subsets, Lang + dDC is the most critical for the generation of robust CD8 + T-cell immunity after s.s. with VACV.