High-Dose Vitamin D3 Supplementation Is a Requisite for Modulation of Skin-Homing Markers on Regulatory T Cells in HIV-infected Patients.

Vitamin ₃ is known to have an effect on the immune function. We investigated the immunomodulatory capability of vitamin ₃ in HIV-infected patients and studied the expression of chemokine receptors on regu-latory T cells (Treg). Vitamin ₃-deficient HIV-l-seropositive subjects were treated with cholecalciferol (vitamin ₃) at a dose of 800IU daily for 3 months (n = 9) or 25,000 IU weekly for 2 months (n = 7). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed for skin-homing (CCR4 and CCR10) and gut-homing (CCR9 and integrin α₄/β₇) marker expression on Treg, by flow cytometry, before and after supplementation. Serum 25(OH)₃ and parathyroid hormone (PTH) levels were determined at baseline and after the treatment period. Weekly doses of 25,000 IU cholecalciferol effectively achieved the optimal target serum 25(OH)₃ con-centration of >75nmol/liter (30ng/ml) in HIV-infected patients. High-dose cholecalciferol supplementation differentially influenced skin-homing markers on Treg with an increased level of CCR10 expression and while a reduction in CCR4 expression level was observed together with a lower percentage of Treg expressing CCR4. For both dosing regimens, there were no significant differences in the expression of gut-homing markers, CCR9, and integrin α₄/β₇. High-dose vitamin ₃ supplementation is needed to reverse vitamin ₃ deficiency in HIV-infected individuals and this results in modulation of skin-homing markers but not gut-homing markers ex-pression on Treg. At a standard dose of 800IU/day, vitamin ₃ is not effective in achieving an optimal 25(OH)₃ concentration in patients with an underlying T cell dysfunction and is unable to exert any immu-nomodulatory effects. [ABSTRACT FROM AUTHOR]