Langerin+ Dermal DC, but not Langerhans cells, are required for effective CD8 mediated immune responses after skin scarification with Vaccinia Virus (VACV)

Abstract

Skin scarification (s.s.) with Vaccinia virus (VACV) is essential for generation of an optimal protective T cell memory immune response. Dendritic Cells (DC), which are professional antigen presenting cells, are required for naïve T cell priming and activation. At least three subsets of skin resident DC have been identified: Langerhans Cells (LC), 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 WT and LC depleted mice controlled the progression of OVA257–264 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 the most critical for the generation of robust CD8+ T cell immunity after s.s. with VACV.