Background Recent studies highlight that Vitamin D (VD) may have an immunomodulatory action on T cells, inhibiting Th-1 and Th-17 response and enhancing Th-2 and 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 peripheral expansion of the CD28- T cells, a subpopulation with peculiar effector activities (high g-IFN production and cytotoxic function), that in Rheumatoid Arthritis has been related to a worse prognosis. At 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.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which activation of autoreactive T and B lymphocytes and alteration of Treg functionality may have a pathogenic role. A great prevalence of VD insufficiency has been described in SLE patients (pts), probably due to the low direct sunlight exposition.
Objectives To verify the effect of VD supplementation on the circulating levels of effector memory T cells (CD45RA+/-CCR7-), Treg cells (CD25highCD127low) and CD28- T cells.
Methods 41 female SLE pts (median age=33 (range 10-90th percentile: 24-41) years; median duration of disease=7 (2-16) years) with a clinically quiescent disease (SLEDAI=4 (0-4)) were enrolled. 20 pts were supplemented with an intensive regimen (IR) of colecalciferol (300.000UI for the first month and 50.000UI/monthly as maintenance), whereas 21 pts were supplemented with a standard regimen (SR) (25.000UI monthly). Phenotypic analysis of peripheral T lymphocyte was evaluated by flow-cytometry at baseline and after every 6 months of treatment.
Results At baseline, no difference emerged in VD levels and among main T-cell subtypes in SLE pts. During the study no flare of disease was recorded. After 6 months of treatment, a significant decrease in the percentage number of Treg cells was observed, independently from the regimen of supplementation (IR: from 8.5 (4.8-14.7) to 6.3 (3.9-14)% of CD4+ T cells; p=0.02; SR: from 7.5 (5.6-11.7) to 6.6 (4.7-9.1)% of CD4+ T cells; p=0.04). Within Treg subtype, an increase in peripheral induced (CCR7-) Treg cells was seen (IR: from 29.7 (15.7-43.1) to 42.9 (13.1-54.6)% of total Treg cells; p=0.04; SR: from 26.3 (16.1-43.1) to 34.8 (24-54.1))% of total Treg cells; p<0.01). After 12 months of treatment, we also observed an increase in the total amount of circulating CD4+CD45RA+CCR7- T cells (IR: from 8 (4-23) to 9 (3-33) cells/μl; p<0.01; SR: from 8 (3-24) to 17 (10-51) cells/μl; p<0.01), whereas a reduction of the CD8+CD28- T cells in SLE pts on SR was seen (from 30.2 (14.6-73.2) to 19.0 (7.4-34.6)% of CD8+ T cells; p=0.01). On the contrary, no significant variation of CD28- T cell-subtypes was observed in IR group. No correlation was observed among the levels of main T-cell subtypes, clinical disease activity and VD levels.
Conclusions VD may have immunomodulatory properties on T cells, acting on Treg, on highly experienced memory and on CD28- T cells differentiation.
Bonelli M, Ann Rheum Dis 2010;69 Suppl 1:i65-66.
Disclosure of Interest None Declared
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