Proc Natl Acad Sci U S A 2002 Apr 2
Meehan TF, DeLuca HF.
Department of Biochemistry, University of Wisconsin, College of Agricultural and Life Sciences, Madison, WI 53706.
In addition to its role in calcium and phosphorous homeostasis, 1alpha,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).