Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
Hum Immunol. 2012 Jul;73(7):693-8. doi: 10.1016/j.humimm.2012.04.019. Epub 2012 Apr 28.
Vitamin D deficiency is adversely associated with diseases characterized by inflammation. The combination of the high incidence of vitamin D deficiency in patients undergoing allogeneic stem cell transplants (SCT) and the potential role of vitamin D deficiency in influencing graft-versus-host disease led us to further characterize the expression of VDR on alloreactive T cells. We hypothesized that vitamin D receptor expression may directly regulate alloreactive T cell responses. To overcome existing limitations in measuring VDR in bulk cellular populations, we developed a flow cytometric assay to measure cytoplasmic VDR in human T cells. Upon stimulation, VDR was expressed extremely early and exhibited sustained upregulation with chronic stimulation. VDR expression was also coupled to cytokine production, proliferation, and ERK1/2 phosphorylation. In addition, VDR exhibited a maturation stage-specific pattern of expression, with greatest expression on cells known to mediate GVHD, naïve and early memory T cells. Alloreactive T cells upregulated VDR, whereas the nonreactive T cells did not. Finally, repletion of vitamin D in vitro was sufficient to significantly reduce alloreactive T cell responses. These data suggest that vitamin D effects on T cells may be important in reducing graft versus host disease (GVHD) in the allogeneic stem cell transplant setting.
维生素 D 缺乏与以炎症为特征的疾病呈负相关。在接受同种异体干细胞移植 (SCT) 的患者中，维生素 D 缺乏的高发率以及维生素 D 缺乏在影响移植物抗宿主病方面的潜在作用，促使我们进一步研究 VDR 在同种异体反应性 T 细胞上的表达。我们假设维生素 D 受体的表达可能直接调节同种异体反应性 T 细胞的反应。为了克服在大量细胞群体中测量 VDR 存在的现有局限性，我们开发了一种流式细胞术测定法来测量人 T 细胞中的胞质 VDR。在刺激后，VDR 极早期表达，并随着慢性刺激持续上调。VDR 的表达还与细胞因子产生、增殖和 ERK1/2 磷酸化相关。此外，VDR 表现出成熟阶段特异性的表达模式，在已知介导移植物抗宿主病的细胞、幼稚和早期记忆 T 细胞上表达最强。同种异体反应性 T 细胞上调 VDR，而非反应性 T 细胞则没有。最后，体外补充维生素 D 足以显著降低同种异体反应性 T 细胞的反应。这些数据表明，维生素 D 对 T 细胞的作用可能在减少同种异体干细胞移植中的移植物抗宿主病 (GVHD) 方面很重要。
