Immune activating and inhibiting effects of calcitriol on γδ T cells and NK cells

The immune modulatory effects of vitamin D and the impact of vitamin D deficiency on various diseases are a subject of current scientific research. However, there are few data directly linking vitamin D to hard endpoints in clinical studies, apart from its well-known effects on bone health. It is therefore of interest, that the effectiveness of the therapeutic antibody rituximab is connected to the vitamin D serum level of patients with B cell lymphomas. Rituximab exerts its effect via antibody dependent cell mediated cytotoxicity (ADCC), with NK cells and γδ T cells acting as effector cells. Here we evaluated and compared how γδ T cells and NK cells are modified by long-term in vitro cultivation with calcitriol, the active metabolite of vitamin D. Peripheral blood mononuclear cells from healthy donors were stimulated in vitro with a combination of zoledronic acid (Zol) and interleukin-2 (IL-2) or with sole IL-2 and different concentrations of calcitriol were added to culture for up to 10 days. Our results confirmed the earlier reports of immune suppressive effects of calcitriol on immune cell proliferation and interferon-γ production. Under certain conditions, in vitro incubation with calcitriol led to an inhibited rituximab-mediated ADCC of Zol/IL-2 stimulated γδ T cells, but to an increased cytotoxic activity of IL-2 stimulated NK cells. This study directly shows immune modulatory activity of calcitriol on the cellular level and links vitamin D to anti-tumoral effects of NK and γδ T cells.