Vitamin D receptor expression controls proliferation of naive CD8+ T cells and development of CD8 mediated gastrointestinal inflammation

Background: Vitamin D receptor (VDR) deficiency contributes to the development of experimental inflammatory bowel disease (IBD) in several different models. T cells have been shown to express the VDR, and T cells are targets of vitamin D. In this article we determined the effects of VDR expression on CD8(+) T cells. Results: VDR KO CD8(+) T cells, but not WT CD8(+) T cells, induced colitis in Rag KO recipients. In addition, co-transfer of VDR KO CD8(+) T cells with naive CD4(+) T cells accelerated colitis development. The more severe colitis was associated with rapidly proliferating naive VDR KO CD8(+) T cells and increased IFN-gamma and IL-17 in the gut. VDR KO CD8(+) T cells proliferated in vitro without antigen stimulation and did not downregulate CD62L and upregulate CD44 markers following proliferation that normally occurred in WT CD8(+) T cells. The increased proliferation of VDR KO CD8(+) cells was due in part to the higher production and response of the VDR KO cells to IL-2. Conclusions: Our data indicate that expression of the VDR is required to prevent replication of quiescent CD8(+) T cells. The inability to signal through the VDR resulted in the generation of pathogenic CD8(+) T cells from rapidly proliferating cells that contributed to the development of IBD.