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Second-generation Langerhans cells originating from epidermal precursors are essential for CD8+ T cell priming.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Feb 15; Vol. 192 (4), pp. 1395-403. Date of Electronic Publication: 2014 Jan 13. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
CD11c Antigen metabolism
Cell Differentiation immunology
Chemokine CCL20 immunology
Clodronic Acid
Dendritic Cells metabolism
Heparin-binding EGF-like Growth Factor
Intercellular Signaling Peptides and Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasmids genetics
Receptors, CCR2 deficiency
Receptors, CCR2 genetics
Receptors, CCR2 immunology
Skin cytology
Skin immunology
CD8-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Giant Cells, Langhans immunology
Lymphocyte Activation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24420922
- Full Text :
- https://doi.org/10.4049/jimmunol.1301143