Meehan Terrence F, DeLuca Hector F
Department of Biochemistry, University of Wisconsin, College of Agricultural and Life Sciences, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5557-60. doi: 10.1073/pnas.082100699. Epub 2002 Apr 2.
In addition to its role in calcium and phosphorous homeostasis, 1 alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] appears to be a modulator of the immune system. Administration of 1,25-(OH)(2)D(3) prevents disease in several autoimmune animal models, including experimental autoimmune encephalomyelitis (EAE). The vitamin D receptor is believed to mediate this activity. Among cells of the immune system, CD8(+) T cells have the highest levels of the vitamin D receptor. Because CD8(+) T cells have been implicated as both suppressors and effectors of the inflammation associated with multiple sclerosis and EAE, we examined the question of whether the 1,25-(OH)(2)D(3) suppression of EAE occurs through a CD8(+) T cell-dependent mechanism. To test this hypothesis, mice that are homozygous knockouts for the alpha chain of the CD8 receptor and have been characterized as lacking functional CD8(+) T cells (CD8(+) -/-) were provided 1,25-(OH)(2)D(3) in their diet before EAE induction. Although CD8(+) -/- mice fed the same diet lacking 1,25-(OH)(2)D(3) have a high incidence of EAE, EAE did not occur in CD8(+) -/- mice fed the diet containing 1,25-(OH)(2)D(3). We conclude that CD8(+) T cells neither are needed nor do they play a role in the prevention of EAE by 1,25-(OH)(2)D(3).
除了在钙和磷稳态中发挥作用外，1α,25 - 二羟基维生素D(3)[1,25-(OH)₂D₃]似乎还是免疫系统的调节剂。给予1,25-(OH)₂D₃可预防多种自身免疫动物模型中的疾病，包括实验性自身免疫性脑脊髓炎（EAE）。维生素D受体被认为介导了这种活性。在免疫系统的细胞中，CD8⁺T细胞的维生素D受体水平最高。由于CD8⁺T细胞被认为既是与多发性硬化症和EAE相关炎症的抑制因子又是效应因子，我们研究了1,25-(OH)₂D₃对EAE的抑制是否通过CD8⁺T细胞依赖性机制发生的问题。为了验证这一假设，在诱导EAE之前，给CD8受体α链纯合敲除且被鉴定为缺乏功能性CD8⁺T细胞（CD8⁺ - / -）的小鼠在饮食中提供1,25-(OH)₂D₃。虽然喂食不含1,25-(OH)₂D₃相同饮食的CD8⁺ - / -小鼠EAE发病率很高，但喂食含1,25-(OH)₂D₃饮食的CD8⁺ - / -小鼠并未发生EAE。我们得出结论，CD8⁺T细胞对于1,25-(OH)₂D₃预防EAE既不是必需的，也不发挥作用。
