Intrinsic requirement for the vitamin D receptor in the development of CD8??-expressing T cells.

ABSTRACT: Vitamin D and vitamin D receptor (VDR) deficiency results in severe symptoms of experimental inflammatory bowel disease in several different models. The intraepithelial lymphocytes of the small intestine contain large numbers of CD8??(+) T cells that have been shown to suppress the immune response to Ags found there. In this study, we determined the role of the VDR in the development of CD8??(+) T cells. There are fewer total numbers of TCR??(+) T cells in the gut of VDR knockout (KO) mice, and that reduction was largely in the CD8??(+) TCR??(+) cells. Conversely TCR??(+) T cells were normal in the VDR KO mice. The thymic precursors of CD8??(+) TCR??(+) cells (triple-positive for CD4, CD8??, and CD8??) were reduced and less mature in VDR KO mice. In addition, VDR KO mice had a higher frequency of the CD8??(+) TCR??(+) precursors (double-negative [DN] TCR??(+) T cells) in the gut. The proliferation rates of the DN TCR??(+) gut T cells were less in the VDR KO compared with those in wild type. Low proliferation of DN TCR??(+) T cells was a result of the very low expression of the IL-15R in this population of cells in the absence of the VDR. Bone marrow transplantation showed that the defect in VDR KO CD8??(+) TCR??(+) cells was cell intrinsic. Decreased maturation and proliferation of CD8??(+) TCR??(+) cells in VDR KO mice results in fewer functional CD8??(+) TCR??(+) T cells, which likely explains the increased inflammation in the gastrointestinal tract of VDR KO and vitamin D-deficient mice.

SUBMITTER: Bruce D 

PROVIDER: S-EPMC3127166 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature