Murine Langerin + dermal dendritic cells prime CD 8 + T cells while L angerhans cells induce cross‐tolerance

Abstract

Skin dendritic cells ( DC s) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DC s via the C ‐type lectin Langerin/ CD 207 are cross‐presented to CD 8 + T cells in vivo . We investigated the relative roles of Langerhans cells ( LC s) and Langerin + dermal DC s ( dDC s) in different vaccination settings. Poly(I:C) and anti‐ CD 40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin ( OVA )‐coupled anti‐Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDC s, but not LC s. In chimeric mice where Langerin targeting was restricted to dDC s, CD 8 + T ‐cell memory was enhanced. Conversely, providing Langerin/ OVA exclusively to LC s failed to prime cytotoxicity, despite initial antigen cross‐presentation to CD 8 + T cells. Langerin/ OVA combined with imiquimod could not prime CD 8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LC s. Altogether, Langerin + dDC s prime long‐lasting cytotoxic responses, while cross‐presentation by LC s negatively influences CD 8 + T ‐cell priming. Moreover, this highlights that DC s exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs. image The properties of two murine skin antigen‐presenting dendritic cell ( DC ) subsets were investigated in vivo . Following adjuvanted OVA ‐immunization, functional differences were found between the DC subsets that may bear translational relevance for vaccination in the skin. Both Langerin + dermal DC s and epidermal Langerhans cells ( LC ) can present exogenous antigen to CD 8 + T cells. Langerin + dermal DC s prime long‐lasting cytotoxic responses, while cross‐presentation by LC s negatively influences CD 8 + T‐cell priming. Specific adjuvants can be used to independently harness the different potential of distinct DC subsets simultaneously targeted by an antigen. Treatment of skin with imiquimod, an agonist of TLR 7, does not result in potent immune responses when the antigen is targeted to Langerin, thereby relativizing the paradigm stating that mature DC s always promote immunity.