Second-generation Langerhans cells originating from epidermal precursors are essential for CD8+ T cell priming

Mazal Elnekave, Karina Furmanov, Yaffa Shaul, Tal Capucha, Luba Eli-Berchoer, Katya Zelentsova, Björn E. Clausen, Avi Hai Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8+ T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8+ T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8+ T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node-resident DCs. Intriguingly, CD8 + T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR2-/- mice, or local neutralization of CCL20. This suggests that local, rather than blood-derived, DC precursors mediate CD8+ T cell priming. Analysis of DC differentiation in the immunized skin revealed a gradual increase in the number of CD11c+ cells, which reached their maximum 2 wk after immunization. A similar differentiation kinetics was observed for LCs, with the majority of differentiating LCs proliferating in situ from epidermal precursors. By using B6/Langerin-diphtheria toxin receptor chimeric mice and LC ablation, we demonstrated that epidermal LCs were crucial for the elicitation of CD8 + T cell responses in vivo. Furthermore, LCs isolated from lymph nodes 2 wk after immunization contained the immunization plasmid and directly activated Ag-specific CD8+ T cells ex vivo. Thus, these results indicate that second-generation Ag-expressing LCs differentiating from epidermal precursors directly prime CD8+ T cells and are essential for optimal cellular immune responses following immunization with plasmid DNA.

Original languageAmerican English
Pages (from-to)1395-1403
Number of pages9
JournalJournal of Immunology
Volume192
Issue number4
DOIs
StatePublished - 15 Feb 2014

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