Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus.

ABSTRACT: 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 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 is the most critical for the generation of robust CD8+ T-cell immunity after s.s. with VACV.

SUBMITTER: Seneschal J 

PROVIDER: S-EPMC3945525 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature