Journal
IMMUNOLOGY
Volume 134, Issue 4, Pages 459-468Publisher
WILEY
DOI: 10.1111/j.1365-2567.2011.03507.x
Keywords
1,25-dihydroxyvitamin D-3; cholecalciferol; forkhead box protein 3; HIV; immunomodulation; regulatory T cells
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Funding
- Nutricia Research Foundation, the Netherlands
- Netherlands Organization for Scientific Research
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Vitamin D-3 is known to induce regulatory T (Treg) cells by rendering antigen-presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-di-hydroxyvitamin D-3 [1,25(OH)(2)D-3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up-regulated following anti-CD3/CD28-bead stimulation. 1,25(OH)(2)D-3 inhibited proliferation of Treg cells even when exogenous interleukin-2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)(2)D-3 than conventional T cells. 1,25(OH)(2)D-3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin-10-secreting cells. The cell-division-inhibiting effect of 1,25(OH)(2)D-3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D-3). Increased serum 1,25(OH)(2)D-3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3(+) Treg cell population. In conclusion, 1,25(OH)(2)D-3 directly affects Treg cell growth and promotes interleukin-10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)(2)D-3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.
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