Lymph node resident rather than skin-derived dendritic cells initiate specific T cell responses after Leishmania major infection.
Langerhans cells have been thought to play a major role as APCs for induction of specific immune responses to Leishmania major. Although their requirement for control of infection has been challenged recently, it remains unclear whether they can transport Ag to lymph nodes and promote initiation of T cell responses. Moreover, the role of dermal dendritic cells (DCs), another population of skin DCs, has so far not been addressed. We have investigated the origin and characterized the cell population responsible for initial activation of L. major-specific T cells in susceptible and resistant mice. We found that Ag presentation in draining lymph nodes peaks as early as 24 h after infection and is mainly mediated by a population of CD11c(high)CD11b(high)Gr-1-CD8-langerin- DCs residing in lymph nodes and acquiring soluble Ags possibly drained through the conduit network. In contrast, skin-derived DCs, including Langerhans cells and dermal DCs, migrated poorly to lymph nodes and played a minor role in early T cell activation. Furthermore, prevention of migration through early removal of the infection site did not affect Ag presentation by CD11c(high) CD11b(high) DCs and activation of Leishmania major-specific naive CD4+ T cells in vivo.
Iezzi
Giandomenica
G
Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistrasse 27, 8952 Zürich-Schlieren, Switzerland. iezzi@env.ethz.ch
Fröhlich
Anja
A
Ernst
Bettina
B
Ampenberger
Franziska
F
Saeland
Sem
S
Glaichenhaus
Nicolas
N
Kopf
Manfred
M
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis; D039521:CD11c Antigen / Q000096:biosynthesis; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*
D000953:Antigens, Protozoan; D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine