Open AccessMurine Langerin + dermal dendritic cells prime CD 8 + T cells while L angerhans cells induce cross‐tolerance
Author(s) -
Flacher Vincent,
Tripp Christoph H,
Mairhofer David G,
Steinman Ralph M,
Stoitzner Patrizia,
Idoyaga Juliana,
Romani Nikolaus
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201303283
Subject(s) - langerin , cytotoxic t cell , immunology , c type lectin , dendritic cell , antigen , t cell , antigen presentation , chemistry , priming (agriculture) , antigen presenting cell , biology , cross presentation , microbiology and biotechnology , immune system , in vitro , biochemistry , botany , germination
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.