Department of Laboratory Medicine, Laboratory Medical Immunology, Nijmegen, The Netherlands.
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.
维生素 D3 通过使抗原呈递细胞具有耐受性来诱导调节性 T（Treg）细胞，但其对人类天然 Treg 细胞的直接作用尚不清楚。在这里，我们研究了 1,25-二羟维生素 D（3）[1,25（OH）2D3]是否以及如何直接影响体外人类天然 Treg 细胞的增殖和功能。首先，我们证明这些 Treg 细胞表达维生素 D 受体，这些受体在抗 CD3/CD28 珠刺激后上调。即使提供外源性白细胞介素-2，1,25（OH）2D3 也抑制 Treg 细胞的增殖。Treg 细胞比常规 T 细胞更容易受到 1,25（OH）2D3 的抑制作用。1,25（OH）2D3 既不影响 Treg 细胞的无反应状态也不影响其抑制功能，但诱导了白细胞介素-10 分泌细胞的轻微增加。通过给维生素 D 缺乏的 HIV-1 感染患者补充 2000 IU 胆钙化醇（维生素 D3），在体内也证明了 1,25（OH）2D3 对 Treg 细胞的细胞分裂抑制作用。增加的血清 1,25（OH）2D3 水平与 Treg 细胞的数量和百分比下降有关，这可能归因于增殖 Foxp3+Treg 细胞群的减少。总之，1,25（OH）2D3 直接影响 Treg 细胞的生长并促进白细胞介素-10 的产生，而对激活状态和抑制表型没有明显影响，而在体内，高血清 1,25（OH）2D3 水平与 Treg 细胞增殖减少和 Treg 细胞数量减少有关。
