title: Vitamin D receptor expression controls proliferation of naïve CD8+ T cells and development of CD8 mediated gastrointestinal inflammation.
abstract: 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 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.
  
  
  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.
authors: Jing
authors: J
authors: Chen
authors: Danny
authors: D
authors: Bruce
authors: Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA. mxc69@psu.edu.
authors: Margherita T
authors: MT
authors: Cantorna
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D018167:Receptors, Calcitriol; D017493:Leukocyte Common Antigens