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1,25‐Dihydroxyvitamin D 3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen‐presenting cells
Author(s) -
Khoo AiLeng,
Joosten Irma,
Michels Meta,
Woestenenk Rob,
Preijers Frank,
He XueHui,
Netea Mihai G.,
van der Ven André J. A. M.,
Koenen Hans J. P. M.
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03507.x
Subject(s) - foxp3 , biology , vitamin d and neurology , cell growth , population , antigen , cd28 , t cell , immunology , il 2 receptor , microbiology and biotechnology , endocrinology , medicine , immune system , biochemistry , environmental health
Summary 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‐dihydroxyvitamin 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.