Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D₃

In addition to its role in bone metabolism, vitamin D₃ exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D₃ levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity. We studied the seasonal fluctuation of γδ T cells, the possible influence of vitamin D₃, and the effect of the active metabolite 1α,25(OH)₂D₃ on the in vitro activation of human γδ T cells. In a retrospective analysis with 2625 samples of random blood donors, we observed higher proportions of γδ T cells in winter when compared with summer. In a prospective study over one year with a small cohort of healthy adults who did or did not take oral vitamin D₃ supplementation, higher proportions of γδ T cells were present in donors without oral vitamin D₃ uptake, particularly in spring. However, γδ T cell frequency in blood did not directly correlate with serum levels of 25(OH)D₃. The active metabolite 1α,25(OH)₂D₃ inhibited the in vitro activation of γδ T cells at the level of proliferation, cytotoxicity, and interferon-γ production. Our study reveals novel insights into the seasonal fluctuation of γδ T cells and the immunomodulatory effects of vitamin D₃.