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Glycolipids Injected into the Skin Are Presented to NKT Cells in the Draining Lymph Node Independently of Migratory Skin Dendritic Cells¹

Christoph H. Tripp^*, Florian Sparber^*, Ian F. Hermans, Nikolaus Romani^* and Patrizia Stoitzner^2,*

^* Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria; and Malaghan Institute of Medical Research, Wellington, New Zealand

APCs, such as dendritic cells (DC), can present glycolipid Ags on CD1d molecules to NKT cells. This interaction activates DC and NKT cells, leading to release of cytokines and enhanced T cell responses. Thus, glycolipid Ags are currently being tested as adjuvants for immunotherapy. We were interested in the interaction of murine skin DC with NKT cells in skin-draining lymph nodes. We observed that all skin DC subsets expressed CD1d upon migration to the lymph nodes. Moreover, skin DC were able to present the synthetic glycolipid Ag -galactosylceramide (-GalCer) to the NKT cell hybridoma DN32.D3. Intradermally injected -GalCer was presented by migratory skin DC and lymph node DC to NKT hybridoma cells in vitro. When we injected -GalCer intradermally into the skin, the numbers of various leukocyte subsets in the draining lymph nodes did not change significantly. However, T and B cells as well as NKT cells up-regulated the activation marker CD69. Coapplication of -GalCer with the tumor model Ag OVA induced strong cytolytic CD8⁺ T cell function that could inhibit the growth of B16 melanoma cells expressing OVA. However, mice that were devoid of migratory skin DC developed similar cytotoxic immune responses after intradermal immunization, indicating that skin DC are not required for the adjuvant properties of NKT cell activation and Ag presentation by this immunization route. In conclusion, migratory skin DC are able to interact with NKT cells; however, intradermally applied glycolipids are presented predominantly by lymph node DC to NKT cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by research grants from Innsbruck Medical University (MFI-9442 to P.S.; IFTZ-11 to F.S.) and the Austrian Science Fund (FWF-L120-B13 to C.H.T.). Temporary support for C.H.T. came from Center of Excellence in Medicine and IT/Kompetenzzentrum Medizin Tirol, project 3b. I.F.H. was supported by a New Zealand Health Research Council Sir Charles Hercus Fellowship.

² Address correspondence and reprint requests to Dr. Patrizia Stoitzner, Department of Dermatology and Venerology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail address: Patrizia.Stoitzner{at}i-med.ac.at

³ Abbreviations used in this paper: DC, dendritic cell; -GalCer, -galactosylceramide; CMTMR, chloromethyl-benzoyl-aminotetramethyl-rhodamine; DTR, diphtheria toxin receptor; EGFP, enhanced GFP; LC, Langerhans cell; Ep-CAM, epithelial cell adhesion molecule.