Calcitriol and T cell Function

Kickler K, Ni Choileain S, Williams A, Richards A, Astier AL. Calcitriol Modulates the CD46 Pathway in T Cells. PLoS One. 2012;7(10):e48486. Epub 2012 Oct 29.

The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)(2)D(3) or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFN╬│ ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS

This study shows that the active ingredient of vitamin D (calcitriol) can have an influence on immune function. In healthy T cells they found that calcitriol induced stimulated with CD46 T cells to express markers consistent with Tr1, which is a regulatory T cell producing lots of IL-10, which can inhibit disease-causing T cell function. In MSers, CD25 which is a marker of regulatory T cells or activated T cells when down rather than up as found in healthy cell donors. There is an implication that this means vitamin D supplementation may be good for inhibiting the damaging immune response.Why were MSers different, were they already supplementing with vitamin D? We do not know because we were not told. However, I am not sure what to make of this. The study examined the effect of one dose of calcitriol based on another paper, this was about 100nM of compound. However in health, the blood level is only about 30-40ng/L which is about 0.1nM so a thousand times less. Will Vitamin D supplementation give such a level? I am not sure it does.