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Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo

Nature Immunology volume 4, pages 907–912 (2003)Cite this article

A Corrigendum to this article was published on 01 October 2003

Abstract

Dendritic cells (DCs) are key regulators of immune responses that activate naive antigen-specific T lymphocytes. In draining lymph nodes, antigen-bearing DCs are reported to be rare and short-lived. How such small numbers of short-lived DCs can activate rare antigen-specific T cells is unclear. Here we show that after immunization of mouse skins by gene gun, the number of antigen-bearing DCs that migrate to draining lymph node is 100-fold higher than previously estimated and that they persist for approximately 2 weeks. The substantial frequency and longevity of DCs in situ ensures ample antigen presentation and stimulation for the rare antigen-specific T cells in draining lymph nodes.

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Figure 1: Cutaneous bombardment of ROSA26R mice with pCMV-Cre plasmid DNA marks CD11c+ DCs that migrate to draining lymph nodes.
Figure 2: Phenotype of β-gal+ DCs.
Figure 3: β-gal marking of DCs results from direct transfection of DCs with Cre recombinase–encoding plasmid DNA, not passive uptake of Cre recombinase or β-gal protein.
Figure 4: Kinetics and persistence of β-gal marked DCs in draining lymph nodes after immunization by gene gun.
Figure 5: Antigen-bearing DCs in the draining lymph nodes present vaccine-encoded OVA DNA to OVA-specific CD4 T cells ex vivo.

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Acknowledgements

The authors thank R. Germain for advice; B. Pulendran and members of the Jacob laboratory for discussions; and I. Williams and P. Lambeth for human keratinocyte transgenic construct. J.A.K. was supported by grants from the Foundation Fighting Blindness, the National Eye Institute (National Institutes of Health; EY13459 and P30 EYO06360), and a gift from M. and M. Powell. J.W. was supported by a National Research Service Award grant (F32 EY06985) from the National Eye Institute. J.J. was supported by National Institutes of Health grant AI RO1524751.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Vaccine Research Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, 30322, Georgia, USA

    Sanjay Garg, Alp Oran, Charles H Maris & Joshy Jacob

  2. Department of Ophthalmology, Emory University, Atlanta, 30322, Georgia, USA

    Janine Wajchman & Judith A Kapp

  3. Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo, 182-0002, Japan

    Shin Sasaki

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Correspondence to Joshy Jacob.

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Garg, S., Oran, A., Wajchman, J. et al. Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo. Nat Immunol 4, 907–912 (2003). https://doi.org/10.1038/ni962

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