1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells

Immunology. 2011 Dec;134(4):459-68. doi: 10.1111/j.1365-2567.2011.03507.x.


Vitamin D3 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-dihydroxyvitamin D(3) [1,25(OH)2D3] 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)2D3 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)2D3 than conventional T cells(.) 1,25(OH)2D3 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)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 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)2D3 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)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells* / drug effects
  • Antigen-Presenting Cells* / immunology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • HIV Infections / complications
  • HIV Infections / immunology
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Lymphocyte Activation / drug effects
  • Receptors, Calcitriol / biosynthesis
  • Receptors, Calcitriol / immunology
  • T-Lymphocytes, Regulatory* / drug effects
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / immunology
  • Vitamin D / pharmacology
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / immunology


  • Interleukin-2
  • Receptors, Calcitriol
  • Interleukin-10
  • Vitamin D
  • 1,25-dihydroxyvitamin D