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*Leishmaniasis
The Journal of Immunology, 2006, 177: 1250-1256.
Copyright © 2006 by The American Association of Immunologists

Lymph Node Resident Rather Than Skin-Derived Dendritic Cells Initiate Specific T Cell Responses after Leishmania major Infection

Giandomenica Iezzi2,*, Anja Fröhlich*, Bettina Ernst*, Franziska Ampenberger*, Sem Saeland{dagger}, Nicolas Glaichenhaus{ddagger} and Manfred Kopf2,*

* Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology, Zürich-Schlieren, Switzerland; {dagger} Laboratory for Immunological Research, Schering-Plough, Dardilly, France; and {ddagger} Institut National de la Santé et de la Recherche Medicale, University of Nice-Sophia Antipolis, Valbonne, France

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 CD11chighCD11bhighGr-1CD8langerin 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 CD11chigh CD11bhigh DCs and activation of Leishmania major-specific naive CD4+ T cells in vivo.




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