title: Intrinsic requirement for the vitamin D receptor in the development of CD8αα-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 CD8αα(+) 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 CD8αα(+) T cells. There are fewer total numbers of TCRαβ(+) T cells in the gut of VDR knockout (KO) mice, and that reduction was largely in the CD8αα(+) TCRαβ(+) cells. Conversely TCRγδ(+) T cells were normal in the VDR KO mice. The thymic precursors of CD8αα(+) TCRαβ(+) cells (triple-positive for CD4, CD8αα, and CD8αβ) were reduced and less mature in VDR KO mice. In addition, VDR KO mice had a higher frequency of the CD8αα(+) TCRαβ(+) precursors (double-negative [DN] TCRαβ(+) T cells) in the gut. The proliferation rates of the DN TCRαβ(+) gut T cells were less in the VDR KO compared with those in wild type. Low proliferation of DN TCRαβ(+) 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 CD8αα(+) TCRαβ(+) cells was cell intrinsic. Decreased maturation and proliferation of CD8αα(+) TCRαβ(+) cells in VDR KO mice results in fewer functional CD8αα(+) TCRαβ(+) T cells, which likely explains the increased inflammation in the gastrointestinal tract of VDR KO and vitamin D-deficient mice.
authors.affiliation: Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Bruce
authors.forename: Margherita T
authors.initials: MT
authors.lastname: Cantorna
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000502:physiology*
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018167:Receptors, Calcitriol