Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective
effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of
Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple
sclerosis. In this study, we measured 1,25 (OH)2 Vitamin D and 25 (OH) Vitamin D levels in multiple sclerosis patients
separated into different clinical subgroups according to disease status. In addition, direct effects of 1,25 (OH)2 Vitamin D on
ex vivo CD4+ T cells and myelin-peptide specific T cell lines were investigated to gain more insight into putative regulatory
mechanisms in the disease pathogenesis. One hundred and thirty-two Hispanic patients with clinically definite multiple sclerosis
were studied, 58 with relapsing remitting multiple sclerosis during remission, 34 during relapse and 40 primary progressive
multiple sclerosis cases. Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender
served as controls. Levels of 25(OH)D3 and 1,25(OH)2D3, measured by ELISA were significantly lower in relapsing–remitting
patients than in controls. In addition, levels in patients suffering relapse were lower than during remissions. In contrast, primary
progressive patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific
T cells was significantly inhibited by 1,25(OH)2D3. Moreover, activated Vitamin D enhanced the development of IL-10 producing
cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, Vitamin D receptor expression was induced
by 1,25(OH)2D3 in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH)D3 into biologically
active 1,25(OH)2D3, since T cells express a1-hydroxylase constitutively. Finally, 1,25(OH)2D3 also increased the expression
and biological activity of indoleamine 2,3-dioxygenase, mediating significant increase in the number of CD4+CD25+ T regulatory
cells. Collectively, these data suggest that 1,25(OH)2D3 plays an important role in T cell homeostasis during the course
of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.

http://brain.oxfordjournals.org/content/132/5/1146.full.pdf