Background/Purpose

Vitamin D (VD) receptor is constitutively expressed on the membrane of multiple cells, including lymphocytes. Recent studies highlight that VD may have an action on T cells, inhibiting Th1 and Th17 response and enhancing Th2 and T regulatory (Treg) function.

After repeated antigenic presentation, T cells undergo different functional and phenotypical modifications, leading to the differentiation into highly experienced memory T cells (CD45RA+CCR7-). Similarly, the down-modulation of CD28 may lead to the expansion of the CD28- T cells, a subpopulation with peculiar effector activities (high γ-IFN production and cytotoxic function).

As the best of our knowledge, little is known about the effect of VD on CD28- T cell population and in the differentiation of memory T cells.

The aim of this study is to verify the effect of VD on the circulating levels of T cells in a cohort of SLE patients (pts).

Methods

34 SLE pts were followed-up for 24 months. In the first year, 16 pts (group 1) were supplemented with an intensive regimen of colecalcipherol (300.000UI for the first month and 50.000UI/monthly as maintenance), whereas 18 (group 2) were supplemented with a standard regimen (25.000UI monthly).

During the second year, patients switched to the other regimen.

Phenotypic analysis of peripheral T lymphocyte and the quantification of the intracytoplasmatic production of IL-4 and γ-IFN from peripheral blood mononuclear cells (PBMC) was evaluated by flow-cytometry.

Wilcoxon-signed rank test and Mann-Whitney test were used for the comparisons.

Results

At baseline, no significant difference emerged in VD levels and among main T cell subtypes in SLE pts, with the exception of CD8+CD28- T cells which were expanded in group 1 (group 1 vs. 2, 74.5 vs. 26.6 % of CD8+ T cells; p<<0.01). These pts had a greater serological disease activity (group 1 vs. 2, antidsDNA= 16.6 vs. 4.1 UI/ml; p=0.02).

After 24 months, an increase of the absolute number of Treg cells (CD4+CD25highCD127low) was observed, independently from the regimen of supplementation. Over two years of treatment, a progressive increase in peripheral induced (CCR7-) Treg cells and in the total amount of CD4+CD45RA+CCR7- T cells was seen in both groups, whereas a gradual significant reduction of the CD8+CD28- T cells was observed only in group 2 (table 1-2).

In the group 1, PBMCs of 8 pts were evaluated for cytokines production at baseline and after 12 months of treatment: a reduction of γ-IFN/IL-4 (from 12.1 to 3.2; p=0.01) among CD8+ T cells was detected.

Conclusion

VD may promote the enhancement of peripheral induced Treg cells and the production of Th2 cytokines. Further studies will be necessary to understand the role of highly experienced memory T cells and of CD28- T cells. In our cohort, the expansion of CD8+CD28- T cells may reflect a greater serological activity in SLE pts.