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Department of Dermatology, University Kiel, Kiel, Germany
UV radiation-induced regulatory T cells (UV-Treg) inhibit the sensitization but not the elicitation of contact hypersensitivity when injected i.v. Because UV-Treg express the lymph node homing receptor CD62 ligand, upon i.v. injection they migrate into the lymph nodes but not into the periphery and therefore inhibit sensitization but not elicitation. We tried to modify the migratory behavior of UV-Treg with the aim to get them into the periphery and thereby to suppress the effector phase of immune reactions. Because the tissue selective homing of T effector cells is determined by tissue-specific dendritic cells (DC), we attempted to reprogram the migratory behavior of UV-Treg by DC. 2,4-Dinitrofluorobencene (DNFB)-specific UV-Treg coincubated with epidermal Langerhans cells (LC) blocked the elicitation upon i.v. injection into DNFB-sensitized mice. In contrast, i.v. injection of UV-Treg not incubated with LC did not inhibit the ear challenge. The same negative effect was observed for UV-Treg coincubated with DC from bone marrow, spleen, or lymph nodes. This effect was not due to different maturation stages as checked by MHC class II expression of the different DC types. Incubation with LC but not with bone marrow-derived DC down-regulated the expression of CD62 ligand on UV-Treg. Accordingly, CFDA-SE labeled UV-Treg coincubated with LC were found in the ears but not in the lymph nodes upon i.v. injection. This finding shows that the migratory behavior can be reprogrammed by tissue-specific DC and may have input on strategies trying to use Treg not only for the prevention but also for the treatment of immune-mediated diseases.
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1 This work was supported by grants from the German Research Foundation (SFB 415, A16; SCHW1177/1-1). T.S. is a recipient of the CERIES 2004 Research Award.
2 A.S. and A.M. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Thomas Schwarz, Department of Dermatology, University Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. E-mail address: tschwarz{at}dermatology.uni-kiel.de
4 Abbreviations used in this paper: CHS, contact hypersensitivity; DC, dendritic cell; BMDC, bone marrow-derived DC; DNFB, 2,4-dintrofluorobencene; CD62L, CD62 ligand; DNBS, dinitrobenzenesulfonic acid-sodium salt; LC, Langerhans cell; Treg, regulatory T cell; PSGL-1, P-selectin glycoprotein ligand-1.
This article has been cited by other articles:
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  A. Maeda, S. Beissert, T. Schwarz, and A. Schwarz Phenotypic and Functional Characterization of Ultraviolet Radiation-Induced Regulatory T Cells J. Immunol., March 1, 2008; 180(5): 3065 - 3071. [Abstract] [Full Text] [PDF]
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