Vitamin D receptor expression controls proliferation of naïve CD8+ T cells and development of CD8 mediated gastrointestinal inflammation
1 Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA
2 Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA
3 Pathobiology Graduate Program, The Pennsylvania State University, University Park, PA 16802, USA
4 Present address: Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
5 Department of Veterinary and Biomedical Sciences, The Center for Molecular Immunology and Infectious Disease, 115 Henning Bldg, University Park, PA 16802, USA
BMC Immunology 2014, 15:6 doi:10.1186/1471-2172-15-6Published: 7 February 2014
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.
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 naïve CD4+ T cells accelerated colitis development. The more severe colitis was associated with rapidly proliferating naïve VDR KO CD8+ T cells and increased IFN-γ 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.
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.