title: 1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells.
abstract: 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.
authors: Department of Laboratory Medicine, Laboratory Medical Immunology, Nijmegen, The Netherlands.
authors: Ai-Leng
authors: AL
authors: Khoo
authors: Irma
authors: I
authors: Joosten
authors: Meta
authors: M
authors: Michels
authors: Rob
authors: R
authors: Woestenenk
authors: Frank
authors: F
authors: Preijers
authors: Xue-Hui
authors: XH
authors: He
authors: Mihai G
authors: MG
authors: Netea
authors: André J A M
authors: AJ
authors: van der Ven
authors: Hans J P M
authors: HJ
authors: Koenen
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000150:complications / Q000276:immunology
chemical_list: D007376:Interleukin-2; D018167:Receptors, Calcitriol; D016753:Interleukin-10; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D