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Updated: Jun 12, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Gene regulation by 1,25-dihydroxyvitamin D3 in CD4+CD25+ cells is enabled by IL-2
Shelley Gorman1, Melinda A Judge, Prue H Hart
1Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia. shelleyg@ichr.uwa.edu.au
Abstract:
Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) enhances the immunoregulatory ability of CD4+CD25+ T cells residing in the skin-draining lymph nodes (SDLNs) of mice. The mechanisms responsible were investigated by examining the expression of 84 cytokine and cytokine-related genes in a 96-well gene array. CD4+CD25+ cells isolated from the SDLNs of BALB/c mice, 24 and 96 hours after topical treatment with 1,25(OH)(2)D(3), consistently expressed increased IL-2 mRNA levels and also secreted enhanced quantities of IL-2 after ex vivo stimulation with phorbol 12-myristate 13-acetate and ionomycin. CD4+CD25+ cells from the lymph nodes of naive mice constitutively express the vitamin D receptor, allowing direct modulation by 1,25(OH)(2)D(3). However, in vitro treatment with 1,25(OH)(2)D(3) did not modify the expression of 84 tested cytokine and cytokine-related mRNAs. It was only in the presence of IL-2 that 1,25(OH)(2)D(3) increased the expression of genes including IL-2 and TLR4. Further, 1,25(OH)(2)D(3) enhanced the ability of IL-2 to stimulate CD4+CD25+ cells to proliferate in vitro and also regulate contact hypersensitivity responses on adoptive transfer into naive mice. Therefore, 1,25(OH)(2)D(3) enabled by IL-2 can directly enhance the regulatory potential of CD4+CD25+ T cells to control immune disease.
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