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Topically Applied 1,25-Dihydroxyvitamin D₃ Enhances the Suppressive Activity of CD4⁺CD25⁺ Cells in the Draining Lymph Nodes¹

Shelley Gorman^*, L. Alexandra Kuritzky^*, Melinda A. Judge^*, Katie M. Dixon, Jacqueline P. McGlade^*, Rebecca S. Mason, John J. Finlay-Jones^* and Prue H. Hart^2,*

^* Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Australia; and Bosch Institute and Department of Physiology, University of Sydney, Australia

The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), the active form of vitamin D. In this study, topically applied 1,25(OH)₂D₃, enhanced the suppressive capacity of CD4⁺CD25⁺ cells from the draining lymph nodes. The effects of topical 1,25(OH)₂D₃ were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)₂D₃ production in skin. CD4⁺ cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)₂D₃-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4⁺CD25⁺ cells. Furthermore, purified CD4⁺CD25⁺ cells from the SDLN of 1,25(OH)₂D₃-treated or UVB-irradiated mice compared with equal numbers of CD4⁺CD25⁺ cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4⁺Foxp3⁺ cells of donor origin significantly increased in recipients of CD4⁺CD25⁺ cells from the SDLN of 1,25(OH)₂D₃-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)₂D₃ may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects.

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 study was supported by the Cancer Council of Western Australia, the National Health and Medical Research Council of Australia, and the University of Western Australia.

² Address correspondence and reprint requests to Dr. Prue Hart, Telethon Institute for Child Health Research, P. O. Box 855, West Perth, Australia. E-mail address: prueh{at}ichr.uwa.edu.au

³ Abbreviations: 1,25(OH)₂D₃, 1,25-dihydroxyvitamin D₃; SDLN, skin-draining lymph nodes; CHS, contact hypersensitivity; PLN, peritoneal cavity-draining lymph nodes; DNFB, 2,4-dinitrofluorobenzene; VDR, vitamin D receptor.